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Sample records for accelerated cerebral white

  1. Cerebral White Matter

    PubMed Central

    Schmahmann, Jeremy D.; Smith, Eric E.; Eichler, Florian S.; Filley, Christopher M.

    2013-01-01

    Lesions of the cerebral white matter (WM) result in focal neurobehavioral syndromes, neuropsychiatric phenomena, and dementia. The cerebral WM contains fiber pathways that convey axons linking cerebral cortical areas with each other and with subcortical structures, facilitating the distributed neural circuits that subserve sensorimotor function, intellect, and emotion. Recent neuroanatomical investigations reveal that these neural circuits are topographically linked by five groupings of fiber tracts emanating from every neocortical area: (1) cortico-cortical association fibers; (2) corticostriatal fibers; (3) commissural fibers; and cortico-subcortical pathways to (4) thalamus and (5) pontocerebellar system, brain stem, and/or spinal cord. Lesions of association fibers prevent communication between cortical areas engaged in different domains of behavior. Lesions of subcortical structures or projection/striatal fibers disrupt the contribution of subcortical nodes to behavior. Disconnection syndromes thus result from lesions of the cerebral cortex, subcortical structures, and WM tracts that link the nodes that make up the distributed circuits. The nature and the severity of the clinical manifestations of WM lesions are determined, in large part, by the location of the pathology: discrete neurological and neuropsychiatric symptoms result from focal WM lesions, whereas cognitive impairment across multiple domains—WM dementia—occurs in the setting of diffuse WM disease. We present a detailed review of the conditions affecting WM that produce these neurobehavioral syndromes, and consider the pathophysiology, clinical effects, and broad significance of the effects of aging and vascular compromise on cerebral WM, in an attempt to help further the understanding, diagnosis, and treatment of these disorders. PMID:18990132

  2. Impaired cerebrovascular hemodynamics are associated with cerebral white matter damage

    PubMed Central

    Purkayastha, Sushmita; Fadar, Otite; Mehregan, Aujan; Salat, David H; Moscufo, Nicola; Meier, Dominik S; Guttmann, Charles RG; Fisher, Naomi DL; Lipsitz, Lewis A; Sorond, Farzaneh A

    2014-01-01

    White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals. PMID:24129749

  3. Microvasculature of the human cerebral white matter: arteries of the deep white matter.

    PubMed

    Nonaka, Hiroko; Akima, Michio; Hatori, Tsutomu; Nagayama, Tadashi; Zhang, Zean; Ihara, Fumie

    2003-06-01

    The vascular architecture of the human cerebral deep white matter was studied using soft X-ray and diaphanized specimens, achieved by intra-arterial injection of barium and vascular stain respectively, and also by electron microscopic examination of the corrosion cast of arteries in normal adult brains. The deep white matter arteries passed through the cerebral cortex with a few branches to the cortex and ran straight through the white matter. The arteries concentrated ventriculopetally to the white matter around the lateral ventricle. Anastomoses were noted around the ventricular wall at the terminals of the deep white matter arteries. No centrifugal branches irrigating the periventricular white matter from the lenticulo-striate arteries were observed in the present study. The presence of anastomoses among the terminal branches of deep white matter arteries protects against ischemic change or infarction in this area from an occlusion of a single deep white matter artery. This may lead to development of terminal zone infarction from ischemia or vascular diseases, affecting multiple deep white matter arteries. The subcortical and deep white matter arteries had thick adventitial sheaths and large adventitial spaces in the white matter but not in the cortex. The presence or absence of the adventitial space is regarded as another characteristic difference between the arteries in the white matter and cortex. This difference may influence pathological changes in vascular lesions in these respective areas. PMID:12777099

  4. Cerebral white matter deficiencies in pedophilic men.

    PubMed

    Cantor, James M; Kabani, Noor; Christensen, Bruce K; Zipursky, Robert B; Barbaree, Howard E; Dickey, Robert; Klassen, Philip E; Mikulis, David J; Kuban, Michael E; Blak, Thomas; Richards, Blake A; Hanratty, M Katherine; Blanchard, Ray

    2008-02-01

    The present investigation sought to identify which brain regions distinguish pedophilic from nonpedophilic men, using unbiased, automated analyses of the whole brain. T1-weighted magnetic resonance images (MRIs) were acquired from men who demonstrated illegal or clinically significant sexual behaviors or interests (n = 65) and from men who had histories of nonsexual offenses but no sexual offenses (n = 62). Sexual interest in children was assessed by participants' admissions of pedophilic interest, histories of committing sexual offenses against children, and psychophysiological responses in the laboratory to erotic stimuli depicting children or adults. Automated parcellation of the MRIs revealed significant negative associations between pedophilia and white matter volumes of the temporal and parietal lobes bilaterally. Voxel-based morphometry corroborated the associations and indicated that the regions of lower white matter volumes followed, and were limited to, two major fiber bundles: the superior fronto-occipital fasciculus and the right arcuate fasciculus. No significant differences were found in grey matter or in cerebrospinal fluid (CSF). Because the superior fronto-occipital and arcuate fasciculi connect the cortical regions that respond to sexual cues, these results suggest (1) that those cortical regions operate as a network for recognizing sexually relevant stimuli and (2) that pedophilia results from a partial disconnection within that network. PMID:18039544

  5. Radioactive microsphere study of cerebral blood flow under acceleration. Technical report

    SciTech Connect

    Greenlees, K.J.; Yoder, J.E.; Toth, D.M.; Oloff, C.M.; Karl, A.

    1980-11-01

    A study using radioactive microspheres for the investigation of cerebral blood flow during acceleration is described. Details of a technique for the blunt dissection of cerebral tissues are included. Results of flow studies at 3 and 5 G sub z acceleration stress indicate there is no selective regional preservation of cerebral tissue. (Author)

  6. Early onset West syndrome with cerebral hypomyelination and reduced cerebral white matter.

    PubMed

    Tohyama, Jun; Akasaka, Noriyuki; Osaka, Hitoshi; Maegaki, Yoshihiro; Kato, Mitsuhiro; Saito, Naka; Yamashita, Sumimasa; Ohno, Kousaku

    2008-05-01

    Numerous numbers of pre-, peri- and postnatal damages cause West syndrome in early infancy, however, etiology in many cases are not still elucidated despite intensive biochemical and neuroradiologic investigations. We described four patients having early onset epileptic encephalopathy with severe hypomyelination and reduction in cerebral white matter. The clinical symptoms of these patients are impaired visual attention, acquired microcephaly, spastic tetraplegia, profound psychomotor delay and infantile spasms since early infancy. All patients had striking hypomyelination of cerebrum, reduced volume of white matter and cortical atrophy on MRI. Serial MRI investigations in three patients showed absence of myelination of the white matter. On EEG, one patient revealed suppression-burst and other three had hypsarrhythmia. Despite having intractable seizures, no patient showed deterioration of neurological development. The group of these findings is mimicking to clinical manifestations of 3-phosphoglycerate dehydrogenase deficiency, and has some overlap with progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) like syndrome, however it is not compatible with these two conditions. The findings observed in our patients can be regarded as a new clinical condition associated with early onset West syndrome. PMID:18065176

  7. Small white matter lesion detection in cerebral small vessel disease

    NASA Astrophysics Data System (ADS)

    Ghafoorian, Mohsen; Karssemeijer, Nico; van Uden, Inge; de Leeuw, Frank E.; Heskes, Tom; Marchiori, Elena; Platel, Bram

    2015-03-01

    Cerebral small vessel disease (SVD) is a common finding on magnetic resonance images of elderly people. White matter lesions (WML) are important markers for not only the small vessel disease, but also neuro-degenerative diseases including multiple sclerosis, Alzheimer's disease and vascular dementia. Volumetric measurements such as the "total lesion load", have been studied and related to these diseases. With respect to SVD we conjecture that small lesions are important, as they have been observed to grow over time and they form the majority of lesions in number. To study these small lesions they need to be annotated, which is a complex and time-consuming task. Existing (semi) automatic methods have been aimed at volumetric measurements and large lesions, and are not suitable for the detection of small lesions. In this research we established a supervised voxel classification CAD system, optimized and trained to exclusively detect small WMLs. To achieve this, several preprocessing steps were taken, which included a robust standardization of subject intensities to reduce inter-subject intensity variability as much as possible. A number of features that were found to be well identifying small lesions were calculated including multimodal intensities, tissue probabilities, several features for accurate location description, a number of second order derivative features as well as multi-scale annular filter for blobness detection. Only small lesions were used to learn the target concept via Adaboost using random forests as its basic classifiers. Finally the results were evaluated using Free-response receiver operating characteristic.

  8. Cerebral white matter correlates of delay discounting in adolescents.

    PubMed

    Ho, Beng-Choon; Koeppel, Julie A; Barry, Amy B

    2016-05-15

    The adolescent brain undergoes extensive structural white matter (WM) changes. Adolescence is also a critical time period during which cognitive, emotional and social maturation occurs in transition into adulthood. Compared to adults, adolescents are generally more impulsive with increased risk-taking behaviors. The goal of this study is to examine whether adolescent impulsivity may be related to cerebral WM maturation. In 89 healthy adolescents, we assessed impulsivity using the delay discounting task, and MRI WM volumes in brain regions previously implicated in delay discounting behaviors. We found that smaller delay discounting AUC (area under the curve) was associated with larger WM volumes in orbitofrontal, dorsolateral and medial prefrontal cortices (PFC) and motor cortex. There were no significant effects of AUC on WM volumes within somatosensory brain regions. In our sample, younger age was significantly associated with greater WM volumes in orbitofrontal and dorsolateral PFC subregions. Even after accounting for age-related effects, preference for immediate rewards (or greater impulsivity) still correlated with larger WM volumes in prefrontal regions known to mediate cognitive control. Our findings lend further support to the notion that reduced brain WM maturity may limit the ability in adolescents to forgo immediate rewards leading to greater impulsivity. PMID:26946275

  9. Increased Number of White Matter Lesions in Patients with Familial Cerebral Cavernous Malformations

    PubMed Central

    Golden, Michael J.; Morrison, Leslie A.; Kim, Helen; Hart, Blaine L.

    2015-01-01

    BACKGKROUND AND PURPOSE Familial cerebral cavernous malformations, an autosomal dominant disorder, result in excess morbidity and mortality in affected patients. The disorder is most prevalent in the Southwest United States, where the affected families are most often carriers of the CCM1-KRIT1 Common Hispanic Mutation. The brain and spinal cord parenchyma in these individuals is usually affected by multiple cavernous malformations. Previous studies have shown abnormalities of endothelial cell junctions and the blood-brain barrier in cerebral cavernous malformations. Endothelial cell abnormalities have also been described in pathologic studies of white matter hyperintensities. We compared the prevalence of white matter hyperintensities in a population with known familial cerebral cavernous malformations. MATERIALS AND METHODS We examined 191 subjects with familial cerebral cavernous malformations who were enrolled into an institutional review board-approved study. All carry the same Common Hispanic Mutation in the CCM1 gene. Each subject underwent 3TMR imaging, including gradient recalled-echo, SWI, and FLAIR sequences. The number of cavernous malformations and the number of nonhemorrhagic white matter hyperintensities were counted. Subjects older than 60 yearsof age were excluded due to the high prevalence of white matter lesions in this population, and children younger than 6 were excluded due to potential sedation requirements. Logistic regression analysis was performed to determine the prevalence of abnormal white matter hyperintensities in those with familial cerebral cavernous malformations compared with healthy controls or those with sporadic cerebral cavernous malformation within the familial cerebral cavernous malformations group; it was also performed to evaluate the associations between abnormal white matter hyperintensities and age, sex, headaches, thyroid disease, diabetes, hypertension, hyperlipidemia, seizure history, or modified Rankin Scale score

  10. MELAS with diffuse degeneration of the cerebral white matter: report of an autopsy case.

    PubMed

    Yokoyama, Teruo; Hasegawa, Kazuko; Obama, Runko; Ishihara, Tadayuki; Yagishita, Saburou

    2010-02-01

    Up to now diffuse white matter demyelination of the cerebrum has been reported in only a few cases of mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS). Here we document an autopsy case with this rare neuropathology. Most MELAS cases are diagnosed antemortem by A3243G transition of mitochondrial DNA. While cerebral damage including necrotic foci in the cerebral cortex are common findings in MELAS, prominent white matter involvement best characterizes this MELAS case. There were numerous necrotic foci, varying in size and chronological stage, in the cerebral white matter. In the areas of the white matter without necrotic foci, there was diffuse fibrillary gliosis with the loss of axons and oligodendrocytes. The gliosis was dominant in the deep white matter, sparing the U-fiber. The cerebral cortex showed diffuse cortical atrophy with few scattered necrotic foci. Distribution of the cerebral lesions does not coincide with the territory of blood supply. The vascular wall presented only slight to mild hyalinosis. We assumed a common pathogenesis to the cortical lesions and the white matter change. The pathogenesis of the present diffuse cerebral lesions may not be just secondary to circulatory disturbance but partly due to metabolic abnormality. PMID:19496942

  11. Accelerator Center: National symbol or white elephant?

    SciTech Connect

    1995-06-02

    This article discusses the possible future of the National Accelerator Center facility in South Africa. This state of the art facility with a 200-megaelectrol-volt proton cyclotron, carries out important nuclear physics research but takes a huge part of South Africa`s total science research budget.

  12. Cerebral White Matter Integrity Mediates Adult Age Differences in Cognitive Performance

    ERIC Educational Resources Information Center

    Madden, David J.; Spaniol, Julia; Costello, Matthew C.; Bucur, Barbara; White, Leonard E.; Cabeza, Roberto; Davis, Simon W.; Dennis, Nancy A.; Provenzale, James M.; Huettel, Scott A.

    2009-01-01

    Previous research has established that age-related decline occurs in measures of cerebral white matter integrity, but the role of this decline in age-related cognitive changes is not clear. To conclude that white matter integrity has a mediating (causal) contribution, it is necessary to demonstrate that statistical control of the white…

  13. Association of Rotavirus With Seizures Accompanied by Cerebral White Matter Injury in Neonates.

    PubMed

    Oh, Ki Won; Moon, Chang Hoon; Lee, Kyung Yeon

    2015-10-01

    We aimed to identify whether rotavirus, human parechovirus, or enterovirus are causative or associated viral pathogens of seizures accompanied by diffuse cerebral white matter injury in neonates. Thirty neonates who presented with seizures and diffusion-restriction in the widespread bilateral cerebral white matter on diffusion-weighted magnetic resonance imaging (MRI) were included in this study. All patients were tested for rotavirus, human parechovirus, and enterovirus by using reverse transcription PCR. Stool, cerebrospinal fluid, and serum samples were examined in 30, 25, and 20 patients, respectively. Rotavirus was detected in stool samples from all 30 patients (100%). Stool samples from 5 patients (16.7%) were also positive for enterovirus. Rotavirus or human parechovirus were not detected in any cerebrospinal fluid samples from 25 patients, but 1 patient tested positive for enterovirus. No virus was detected in any of 20 patient sera. This study indicated an association between rotavirus and seizures accompanied by diffuse cerebral white matter lesions in neonates. PMID:25637646

  14. APOE/TOMM 40 genetic loci, white matter hyperintensities, and cerebral microbleeds

    PubMed Central

    Lyall, Donald M.; Muñoz Maniega, Susana; Harris, Sarah E.; Bastin, Mark E.; Murray, Catherine; Lutz, Michael W.; Saunders, Ann M.; Roses, Allen D.; Valdés Hernández, Maria del C.; Royle, Natalie A.; Starr, John M.; Porteous, David J.; Deary, Ian J.

    2015-01-01

    Background Two markers of cerebral small vessel disease are white matter hyperintensities and cerebral microbleeds, which commonly occur in people with Alzheimer's disease. Aim and/or hypothesis To test for independent associations between two Alzheimer's disease‐susceptibility gene loci – APOE ε and the TOMM 40 ‘523’ poly‐T repeat – and white matter hyperintensities/cerebral microbleed burden in community‐dwelling older adults. Methods Participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε and TOMM 40 523, and detailed structural brain magnetic resonance imaging at a mean age of 72·70 years (standard deviation = 0·7; range = 71–74). Results No significant effects of APOE ε or TOMM 40 523 genotypes on white matter hyperintensities or cerebral microbleed burden were found amongst 624 participants. Conclusions Lack of association between two Alzheimer's disease susceptibility gene loci and markers of cerebral small vessel disease may reflect the relative health of this population compared with those in other studies in the literature. PMID:26310205

  15. Cerebral white matter integrity during primary HIV infection

    PubMed Central

    Wright, Patrick W.; Vaida, Florin F.; Fernández, Ricardo J.; Rutlin, Jerrel; Price, Richard W.; Lee, Evelyn; Peterson, Julia; Fuchs, Dietmar; Shimony, Joshua S.; Robertson, Kevin R.; Walter, Rudolph; Meyerhoff, Dieter J.; Spudich, Serena; Ances, Beau M.

    2016-01-01

    Objective Inflammation and infection within the central nervous system is initiated during primary HIV infection (PHI), but the association of these processes with the integrity of brain white matter during PHI is unknown. Design We used diffusion tensor imaging (DTI) in this prospective cross-sectional neuroimaging study to determine the extent of white matter involvement in early HIV infection. Methods Antiretroviral-naive PHI (defined as <1 year after infection, n = 62), chronic HIV infection (CHI, n = 16), and HIV-uninfected (n = 19) participants had DTI, laboratory, and neuropsychometric performance assessments. DTI metrics were examined using region of interest and whole brain voxelwise analyses. Linear mixed-effects models assessed correlations between DTI measures and laboratory and neuropsychometric performance values. Results PHI participants were assessed at a median 4.1 months after estimated infection, and had median CD4+ cell count of 573 cells/µl, and HIV-1 RNA viral load of 4.5 log10 copies/ml in plasma and 2.6 log10 copies/ml in cerebrospinal fluid (CSF). DTI metrics in PHI individuals were similar to HIV— participants and correlated with disruptions in the blood-brain barrier (indicated by CSF/plasma albumin ratio and CSF protein). CHI participants had significant loss of white matter integrity that correlated with biomarkers of infection and inflammation (blood viral load, CD4+ T-cell count, and neopterin, and CSF white blood cell). Within the PHI group, DTI metrics inversely correlated with increasing days since infection. Conclusion In individuals assessed during PHI, group DTI measures suggested relative preservation of white matter microstructural integrity, but were associated with disruption of the blood-brain barrier and estimated duration of infection. PMID:25513818

  16. Portal-systemic shunt encephalopathy presenting with diffuse cerebral white matter lesion: an autopsy case.

    PubMed

    Kimura, Noriyuki; Kumamoto, Toshihide; Hanaoka, Takuya; Nakamura, Kenichiro; Hazama, Yusuke; Arakawa, Ryuki

    2008-12-01

    We report herein an autopsy case of portal-systemic encephalopathy (PSE) presenting with diffuse tissue rarefaction in the cerebral deep white matter. Clinically, the patient showed recurrent episodes of unconsciousness, abnormal behavior and urinary incontinence, as well as flapping tremor. Cognitive impairment and peripheral neuropathy developed following recurrent episodes. Although conventional arterial portography revealed a small portal-systemic collateral vessel of a left gastro-renal venous shunt, abdominal CT and liver biopsy showed no evidence of liver cirrhosis and serum ammonia level showed a mild increase. T2-weighted MRI demonstrated symmetrical signal hyperintensities in the deep white matter. Neuropathological findings showed Alzheimer type II astrocytes in the deep layers of the cerebral cortices and severe tissue rarefaction with no or slight reactive astrocytosis in the subcortical and deep white matter. These white matter changes have been reported infrequently in patients with PSE. The present case suggests that chronic PSE without liver cirrhosis may develop diffuse white matter lesions. PMID:18384515

  17. Microstructure and Cerebral Blood Flow within White Matter of the Human Brain: A TBSS Analysis

    PubMed Central

    Giezendanner, Stéphanie; Fisler, Melanie Sarah; Soravia, Leila Maria; Andreotti, Jennifer; Walther, Sebastian; Wiest, Roland; Dierks, Thomas; Federspiel, Andrea

    2016-01-01

    Background White matter (WM) fibers connect different brain regions and are critical for proper brain function. However, little is known about the cerebral blood flow in WM and its relation to WM microstructure. Recent improvements in measuring cerebral blood flow (CBF) by means of arterial spin labeling (ASL) suggest that the signal in white matter may be detected. Its implications for physiology needs to be extensively explored. For this purpose, CBF and its relation to anisotropic diffusion was analyzed across subjects on a voxel-wise basis with tract-based spatial statistics (TBSS) and also across white matter tracts within subjects. Methods Diffusion tensor imaging and ASL were acquired in 43 healthy subjects (mean age = 26.3 years). Results CBF in WM was observed to correlate positively with fractional anisotropy across subjects in parts of the splenium of corpus callosum, the right posterior thalamic radiation (including the optic radiation), the forceps major, the right inferior fronto-occipital fasciculus, the right inferior longitudinal fasciculus and the right superior longitudinal fasciculus. Furthermore, radial diffusivity correlated negatively with CBF across subjects in similar regions. Moreover, CBF and FA correlated positively across white matter tracts within subjects. Conclusion The currently observed findings on a macroscopic level might reflect the metabolic demand of white matter on a microscopic level involving myelination processes or axonal function. However, the exact underlying physiological mechanism of this relationship needs further evaluation. PMID:26942763

  18. Detection of white matter lesions in cerebral small vessel disease

    NASA Astrophysics Data System (ADS)

    Riad, Medhat M.; Platel, Bram; de Leeuw, Frank-Erik; Karssemeijer, Nico

    2013-02-01

    White matter lesions (WML) are diffuse white matter abnormalities commonly found in older subjects and are important indicators of stroke, multiple sclerosis, dementia and other disorders. We present an automated WML detection method and evaluate it on a dataset of small vessel disease (SVD) patients. In early SVD, small WMLs are expected to be of importance for the prediction of disease progression. Commonly used WML segmentation methods tend to ignore small WMLs and are mostly validated on the basis of total lesion load or a Dice coefficient for all detected WMLs. Therefore, in this paper, we present a method that is designed to detect individual lesions, large or small, and we validate the detection performance of our system with FROC (free-response ROC) analysis. For the automated detection, we use supervised classification making use of multimodal voxel based features from different magnetic resonance imaging (MRI) sequences, including intensities, tissue probabilities, voxel locations and distances, neighborhood textures and others. After preprocessing, including co-registration, brain extraction, bias correction, intensity normalization, and nonlinear registration, ventricle segmentation is performed and features are calculated for each brain voxel. A gentle-boost classifier is trained using these features from 50 manually annotated subjects to give each voxel a probability of being a lesion voxel. We perform ROC analysis to illustrate the benefits of using additional features to the commonly used voxel intensities; significantly increasing the area under the curve (Az) from 0.81 to 0.96 (p<0.05). We perform the FROC analysis by testing our classifier on 50 previously unseen subjects and compare the results with manual annotations performed by two experts. Using the first annotator results as our reference, the second annotator performs at a sensitivity of 0.90 with an average of 41 false positives per subject while our automated method reached the same

  19. [Cerebral white matter bundle measurements by magnetic resonance imaging].

    PubMed

    Yoshii, F; Duara, R

    1989-04-01

    The width of the anterior whole white matter bundle (AWM), interhemispheric (AWM-TER), and intrahemispheric (AWM-TRA) components at the level of the foramen of Monro on horizontal inversion recovery (IR) magnetic resonance (MR) scans were measured in 32 healthy males. The mean age of subjects were 54.4 +/- 18.8, ranged 25 to 83 years old. MR scans were performed using a 0.5 Tesla superconductive magnet, with inversion time of 400 msec, repetition time of 2.1 sec and echo time of 35 msec. The slice thickness was 10mm. Horizontal maximum internal skull diameter (HISD) at the same level was also measured and normalized values of AWM, AWM-TER, AWM-TRA were calculated by dividing the width of AWM, AWM-TER, AWM-TRA by the width of HISD. When absolute values of each AWM width were compared between right and left sides, there were no differences in AWM and AWM-TER. However, AWM-TRA of the right side was significantly wider than that of the left side (t = 4.28, p less than 0.001). The width of AWM was not correlated with age, but the width of AWM-TER showed a significant decline in the left (r = -0.36, p = 0.04) and non-significant trend to decline in the right side (r = -0.33, p = 0.07). The width of AWM-TRA of the left side was tended to decrease with age. Normalized values of AWM, AWM-TER, AWM-TRA showed a similar results as that of the absolute values. The measurement of the white matter bundle width provide some insights into the connectivity of the brain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2612107

  20. Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

    PubMed

    Bennett, I J; Madden, D J

    2014-09-12

    Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

  1. Early treatment of minocycline alleviates white matter and cognitive impairments after chronic cerebral hypoperfusion

    PubMed Central

    Ma, Jing; Zhang, Jing; Hou, Wei Wei; Wu, Xiao Hua; Liao, Ru Jia; Chen, Ying; Wang, Zhe; Zhang, Xiang Nan; Zhang, Li San; Zhou, Yu Dong; Chen, Zhong; Hu, Wei Wei

    2015-01-01

    Subcortical ischemic vascular dementia (SIVD) caused by chronic cerebral hypoperfusion develops with progressive white matter and cognitive impairments, yet no effective therapy is available. We investigated the temporal effects of minocycline on an experimental SIVD exerted by right unilateral common carotid arteries occlusion (rUCCAO). Minocycline treated at the early stage (day 0–3), but not the late stage after rUCCAO (day 4–32) alleviated the white matter and cognitive impairments, and promoted remyelination. The actions of minocycline may not involve the inhibition of microglia activation, based on the effects after the application of a microglial activation inhibitor, macrophage migration inhibitory factor, and co-treatment with lipopolysaccharides. Furthermore, minocycline treatment at the early stage promoted the proliferation of oligodendrocyte progenitor cells (OPCs) in subventricular zone, increased OPC number and alleviated apoptosis of mature oligodendrocytes in white matter. In vitro, minocycline promoted OPC proliferation and increased the percentage of OPCs in S and G2/M phases. We provided direct evidence that early treatment is critical for minocycline to alleviate white matter and cognitive impairments after chronic cerebral hypoperfusion, which may be due to its robust effects on OPC proliferation and mature oligodendrocyte loss. So, early therapeutic time window may be crucial for its application in SIVD. PMID:26174710

  2. Effects of Surgery and Proton Therapy on Cerebral White Matter of Craniopharyngioma Patients

    SciTech Connect

    Uh, Jinsoo; Merchant, Thomas E.; Li, Yimei; Li, Xingyu; Sabin, Noah D.; Indelicato, Daniel J.; Ogg, Robert J.; Boop, Frederick A.; Jane, John A.; Hua, Chiaho

    2015-09-01

    Purpose: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy. Methods and Materials: Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51 atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect. Results: Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non–surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect. Conclusions: DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally

  3. Intranasal administration of aTf protects and repairs the neonatal white matter after a cerebral hypoxic-ischemic event.

    PubMed

    Guardia Clausi, Mariano; Paez, Pablo M; Campagnoni, Anthony T; Pasquini, Laura A; Pasquini, Juana M

    2012-10-01

    Our previous studies showed that the intracerebral injection of apotransferrin (aTf) attenuates white matter damage and accelerates the remyelination process in a neonatal rat model of cerebral hypoxia-ischemia (HI) injury. However, the intracerebral injection of aTf might not be practical for clinical treatments. Therefore, the development of less invasive techniques capable of delivering aTf to the central nervous system would clearly aid in its effective clinical use. In this work, we have determined whether intranasal (iN) administration of human aTf provides neuroprotection to the neonatal mouse brain following a cerebral hypoxic-ischemic event. Apotransferrin was infused into the naris of neonatal mice and the HI insult was induced by right common carotid artery ligation followed by exposure to low oxygen concentration. Our results showed that aTf was successfully delivered into the neonatal HI brain and detected in the olfactory bulb, forebrain and posterior brain 30 min after inhalation. This treatment successfully reduced white matter damage, neuronal loss and astrogliosis in different brain regions and enhanced the proliferation and survival of oligodendroglial progenitor cells (OPCs) in the subventricular zone and corpus callosum (CC). Additionally, using an in vitro hypoxic model, we demonstrated that aTf prevents oligodendrocyte progenitor cell death by promoting their differentiation. In summary, these data suggest that iN administration of aTf has the potential to be used for clinical treatment to protect myelin and to induce remyelination in demyelinating hypoxic-ischemic events in the neonatal brain. PMID:22736466

  4. Neurovascular coupling, cerebral white matter integrity, and response to cocoa in older people

    PubMed Central

    Hurwitz, Shelley; Salat, David H.; Greve, Douglas N.; Fisher, Naomi D.L.

    2013-01-01

    Objective: To investigate the relationship between neurovascular coupling and cognitive function in elderly individuals with vascular risk factors and to determine whether neurovascular coupling could be modified by cocoa consumption. Methods: Sixty older people (aged 72.9 ± 5.4 years) were studied in a parallel-arm, double-blind clinical trial of neurovascular coupling and cognition in response to 24 hours and 30 days of cocoa consumption. Cognitive measures included Mini-Mental State Examination and Trail Making Test A and B. Neurovascular coupling was measured from the beat-to-beat blood flow velocity responses in the middle cerebral arteries to the N-Back Task. In a subset of MRI-eligible participants, cerebral white matter structural integrity was also measured. Results: Neurovascular coupling was associated with Trails B scores (p = 0.002) and performance on the 2-Back Task. Higher neurovascular coupling was also associated with significantly higher fractional anisotropy in cerebral white matter hyperintensities (p = 0.02). Finally, 30 days of cocoa consumption was associated with increased neurovascular coupling (5.6% ± 7.2% vs −2.4% ± 4.8%; p = 0.001) and improved Trails B times (116 ± 78 seconds vs 167 ± 110 seconds; p = 0.007) in those with impaired neurovascular coupling at baseline. Conclusion: There is a strong correlation between neurovascular coupling and cognitive function, and both can be improved by regular cocoa consumption in individuals with baseline impairments. Better neurovascular coupling is also associated with greater white matter structural integrity. PMID:23925758

  5. Clusterin/Apolipoprotein J immunoreactivity is associated with white matter damage in cerebral small vessel diseases

    PubMed Central

    Craggs, Lucinda; Taylor, Julie; Slade, Janet Y.; Chen, Aiqing; Hagel, Christian; Kuhlenbaeumer, Gregor; Borjesson‐Hanson, Anne; Viitanen, Matti; Kalimo, Hannu; Deramecourt, Vincent; Oakley, Arthur E.

    2015-01-01

    Aim Brain clusterin is known to be associated with the amyloid‐β deposits in Alzheimer's disease (AD). We assessed the distribution of clusterin immunoreactivity in cerebrovascular disorders, particularly focusing on white matter changes in small vessel diseases. Methods Post‐mortem brain tissues from the frontal or temporal lobes of a total of 70 subjects with various disorders including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral amyloid angiopathy (CAA) and AD were examined using immunohistochemistry and immunofluorescence. We further used immunogold electron microscopy to study clusterin immunoreactivity in extracellular deposits in CADASIL. Results Immunostaining with clusterin antibodies revealed strong localization in arterioles and capillaries, besides cortical neurones. We found that clusterin immunostaining was significantly increased in the frontal white matter of CADASIL and pontine autosomal dominant microangiopathy and leukoencephalopathy subjects. In addition, clusterin immunostaining correlated with white matter pathology severity scores. Immunostaining in axons ranged from fine punctate deposits in single axons to larger confluent areas with numerous swollen axon bulbs, similar to that observed with known axon damage markers such as non‐phosphorylated neurofilament H and the amyloid precursor protein. Immunofluorescence and immunogold electron microscopy experiments showed that whereas clusterin immunoreactivity was closely associated with vascular amyloid‐β in CAA, it was lacking within the granular osmiophilic material immunolabelled by NOTCH3 extracelluar domain aggregates found in CADASIL. Conclusions Our results suggest a wider role for clusterin associated with white matter damage in addition to its ability to chaperone proteins for clearance via the perivascular drainage pathways in several disease states. PMID:25940137

  6. White matter tract and glial-associated changes in 5-hydroxymethylcytosine following chronic cerebral hypoperfusion.

    PubMed

    Tsenkina, Yanina; Ruzov, Alexey; Gliddon, Catherine; Horsburgh, Karen; De Sousa, Paul A

    2014-12-10

    White matter abnormalities due to age-related cerebrovascular alterations is a common pathological hallmark associated with functional impairment in the elderly which has been modeled in chronically hypoperfused mice. 5-Methylcytosine (5mC) and its oxidized derivative 5-hydroxymethylcytosine (5hmC) are DNA modifications that have been recently linked with age-related neurodegeneration and cerebrovascular pathology. Here we conducted a pilot investigation of whether chronic cerebral hypoperfusion might affect genomic distribution of these modifications and/ or a Ten-Eleven Translocation protein 2 (TET2) which catalyses hydroxymethylation in white and grey matter regions of this animal model. Immunohistochemical evaluation of sham and chronically hypoperfused mice a month after surgery revealed significant (p<0.05) increases in the proportion of 5hmC positive cells, Iba1 positive inflammatory microglia, and NG2 positive oligodendroglial progenitors in the hypoperfused corpus callosum. In the same white matter tract there was an absence of hypoperfusion-induced alterations in the proportion of 5mC, TET2 positive cells and CC1 positive mature oligodrendrocytes. Correlation analysis across animals within both treatment groups demonstrated a significant association of the elevated 5hmC levels with increases in the proportion of inflammatory microglia only (p=0.01) in the corpus callosum. In vitro studies revealed that 5hmC is lost during oligodendroglial maturation but not microglial activation. Additionally, TET1, TET2, and TET3 protein levels showed dynamic alterations during oligodendroglial development and following oxidative stress in vitro. Our study suggests that 5hmC exhibits white matter tract and cell type specific dynamics following chronic cerebral hypoperfusion in mice. PMID:25305569

  7. Decreased and Increased Anisotropy along Major Cerebral White Matter Tracts in Preterm Children and Adolescents

    PubMed Central

    Ben-Shachar, Michal; Feldman, Heidi M.

    2015-01-01

    Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood. PMID:26560745

  8. Photoperiodic Regulation of Cerebral Blood Flow in White-Footed Mice (Peromyscus leucopus)

    PubMed Central

    Teplitsky, Seth

    2016-01-01

    Abstract Individuals living outside the tropics need to adjust their behavioral and physiological repertoires throughout the year to adapt to the changing seasons. White-footed mice (Peromyscus leucopus) reduce hippocampal volumes, hippocampal-dependent memory function, long-term potentiation, and alter neurogenesis in response to short (winter-like) day lengths (photoperiods). During winter, these mice putatively shunt energy away from the brain to maximize peripheral thermogenesis, immune function, and survival. We hypothesized that these changes in brain function are accompanied by alterations in brain vasculature. We maintained white-footed mice in short (8 h light/16 h dark) or long (16 h light/8 h dark) photoperiods for 8–9 weeks. Mice were then perfused with fluorescein isothiocyanate (FITC)-conjugated tomato (Lycopersicon esculentum) lectin to visualize the perfused cerebrovasculature. Short-day mice reduced hippocampal and cortical capillary density (FITC+ area); vessels isolated from short day-exposed mice expressed higher mRNA levels of the gelatinase matrix metalloproteinase 2 (MMP2). Additionally, short-day mice reduced cerebral blood flow ∼15% compared with their long-day counterparts, as assessed by laser speckle flowmetry. Immunohistochemistry revealed higher levels of MMP2 in the hippocampus of mice maintained in short days compared with long days, potentially contributing to the observed vascular remodeling. These data demonstrate that a discrete environmental signal (i.e., day length) can substantially alter cerebral blood flow in adult mammals. PMID:27570829

  9. Photoperiodic Regulation of Cerebral Blood Flow in White-Footed Mice (Peromyscus leucopus).

    PubMed

    Borniger, Jeremy C; Teplitsky, Seth; Gnyawali, Surya; Nelson, Randy J; Rink, Cameron

    2016-01-01

    Individuals living outside the tropics need to adjust their behavioral and physiological repertoires throughout the year to adapt to the changing seasons. White-footed mice (Peromyscus leucopus) reduce hippocampal volumes, hippocampal-dependent memory function, long-term potentiation, and alter neurogenesis in response to short (winter-like) day lengths (photoperiods). During winter, these mice putatively shunt energy away from the brain to maximize peripheral thermogenesis, immune function, and survival. We hypothesized that these changes in brain function are accompanied by alterations in brain vasculature. We maintained white-footed mice in short (8 h light/16 h dark) or long (16 h light/8 h dark) photoperiods for 8-9 weeks. Mice were then perfused with fluorescein isothiocyanate (FITC)-conjugated tomato (Lycopersicon esculentum) lectin to visualize the perfused cerebrovasculature. Short-day mice reduced hippocampal and cortical capillary density (FITC(+) area); vessels isolated from short day-exposed mice expressed higher mRNA levels of the gelatinase matrix metalloproteinase 2 (MMP2). Additionally, short-day mice reduced cerebral blood flow ∼15% compared with their long-day counterparts, as assessed by laser speckle flowmetry. Immunohistochemistry revealed higher levels of MMP2 in the hippocampus of mice maintained in short days compared with long days, potentially contributing to the observed vascular remodeling. These data demonstrate that a discrete environmental signal (i.e., day length) can substantially alter cerebral blood flow in adult mammals. PMID:27570829

  10. Risk factor analysis of cerebral white matter hyperintensities in children with sickle cell disease.

    PubMed

    van der Land, Veronica; Mutsaerts, Henri J M M; Engelen, Marc; Heijboer, Harriët; Roest, Mark; Hollestelle, Martine J; Kuijpers, Taco W; Nederkoorn, Paul J; Cnossen, Marjon H; Majoie, Charles B L M; Nederveen, Aart J; Fijnvandraat, Karin

    2016-01-01

    Sickle cell disease (SCD) is complicated by silent cerebral infarcts, visible as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). Both local vaso-occlusion, elicited by endothelial dysfunction, and insufficiency of cerebral blood flow (CBF) have been proposed to be involved in the aetiology. We performed an explorative study to investigate the associations between WMHs and markers of endothelial dysfunction and CBF by quantifying WMH volume on 3.0 Tesla MRI. We included 40 children with HbSS or HbSβ(0) thalassaemia, with a mean age of 12.1 ± 2.6 years. Boys demonstrated an increased risk for WMHs (odds ratio 4.5, 95% confidence interval 1.2-17.4), unrelated to glucose-6-phosphate dehydrogenase deficiency. In patients with WMHs, lower fetal haemoglobin (HbF) was associated with a larger WMH volume (regression coefficient = -0.62, R2 = 0.5, P = 0.04). Lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) levels were associated with lower CBF in the white matter (regression coefficient = 0.07, R2 = 0.15, P = 0.03), suggesting that endothelial dysfunction could potentially hamper CBF. The findings of our explorative study suggest that a high level of HbF may be protective for WMHs and that endothelial dysfunction may contribute to the development of WMHs by reducing CBF. PMID:26492630

  11. Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly

    PubMed Central

    Scott, Julia A.; Braskie, Meredith N.; Tosun, Duygu; Thompson, Paul M.; Weiner, Michael; DeCarli, Charles; Carmichael, Owen T.

    2015-01-01

    In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of amyloid burden and VRFs with WMH burden in CN elderly individuals with low to moderate vascular risk. Participants (n = 150) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) received fluid attenuated inversion recovery (FLAIR) MRI at study entry. Total WMH volume was calculated from FLAIR images co-registered with structural MRI. Amyloid burden was determined by cerebrospinal fluid Aβ1-42 levels. Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation. We tested ridge regression models for independent associations and interactions of elevated blood pressure (BP) and amyloid to total WMH volume. We found that greater amyloid burden and a clinical history of hypertension were independently associated with greater WMH volume. In addition, elevated BP modified the association between amyloid and WMH, such that those with either current or past evidence of elevated BP had greater WMH volumes at a given burden of amyloid. These findings are consistent with the hypothesis that cerebral amyloid accumulation and VRFs are independently associated with clinically latent white matter damage represented by WMHs. The potential contribution of amyloid to WMHs should be further explored, even among elderly individuals without cognitive impairment and with limited VRF exposure. PMID:26648866

  12. Fractional Anisotropy of Cerebral White Matter and Thickness of Cortical Gray Matter across the Lifespan

    PubMed Central

    P., Kochunov; DC, Glahn; J., Lancaster; P.M., Thompson; V., Kochunov; B., Rogers; P., Fox; J., Blangero; D.E., Williamson

    2011-01-01

    We examined age trajectories of fractional anisotropy (FA) of cerebral white matter (WM) and thickness of cortical gray matter (GM) in 1,031 healthy human subjects (aged 11-90 years). Whole-brain FA and GM thickness values followed quadratic trajectories with age but the relationship between them was linear, indicating that a putative biological mechanism may explain the non-linearity of their age trajectories. Inclusion of the FA values into the quadratic model of the whole-brain and regional GM thickness changes with age made the effect of the age2 term no longer significant for the whole-brain GM thickness and greatly reduced its significance for regional GM thickness measurements. The phylogenetic order of cerebral myelination helped to further explain the intersubject variability in GM thickness. FA values for the early maturing WM were significantly better (p=10−6) at explaining variability in GM thickness in maturing (aged 11-20) subjects than FA values for the late maturing WM. The opposite trend was observed for aging subjects (aged 40-90) where FA values for the late maturing WM were better (p=10−16) at explaining the variability in GM thickness. We concluded that the non-linearity of the age trajectory for GM thickness, measured from T1-weighted MRI, was partially explained by the heterogeneity and the heterochronicity of the age-related changes in the microintegrity of cerebral WM. We consider these findings as the evidence that the measurements of age-related changes in GM thickness and FA are driven, in part, by a common biological mechanism, presumed to be related to changes in cerebral myelination. PMID:21640837

  13. Pharmacological Effects of Erythropoietin and its Derivative Carbamyl erythropoietin in Cerebral White Matter Injury

    NASA Astrophysics Data System (ADS)

    Liu, Wei

    Periventricular leukomalacia (PVL) is the predominant form of brain injury in the premature infant and the most common cause of cerebral palsy, yet no therapy currently exists for this serious human disorder. As PVL often occurs in preterm infants suffering from cerebral hypoxia/ischemia with or without prior exposure to maternal-fetal infection/inflammation, we used hypoxia/ischemia with or without lipopolysaccharide (LPS) injection, to produce clinically relevant PVL-like lesions in the white matter in postnatal day six (P6) mice. We studied the white matter pathology under different conditions, such as different durations of hypoxia and different doses of LPS, to evaluate the effects of those etiological factors on neonatal white matter injury. Distinct related pathological events were investigated at different time points during the progression of PVL. We used immunohistochemistry, histological analysis, and electron microscopy (EM) to study demylination that occurs in the white matter area, which is consistent with the pathology of human PVL. Previous studies have shown that erythropoietin (EPO) and its derivative carbamylated EPO (CEPO) are neuroprotective in various experimental models of brain injury. However, none of these studies investigated their efficacy against white matter injury using appropriate animal models of PVL. We produced unilateral or bilateral white matter injury in P6 mice using unilateral carotid ligation (UCL) followed by hypoxia (6% oxygen, 35 min) or by UCL/hypoxia plus LPS injection, respectively. We administered a single intraperitoneal (i.p.) dose of EPO or CEPO (5000 IU/kg) immediately after the insult, and found both drugs to provide significant protection against white matter injury in PVL mice compared to vehicle-treated groups. In addition, EPO and CEPO treatments attenuated neurobehavioral dysfunctions in an acute manner after PVL injury. EPO and CEPO have relatively few adverse effects, and thus may be a therapeutic agent

  14. Unbiased Stereological Analysis of Reactive Astrogliosis to Estimate Age-Associated Cerebral White Matter Injury.

    PubMed

    McNeal, David W; Brandner, Dieter D; Gong, Xi; Postupna, Nadia O; Montine, Thomas J; Keene, C Dirk; Back, Stephen A

    2016-06-01

    Cerebral white matter injury (WMI) contributes to cognitive dysfunction associated with pathological aging. Because reactive astrocyte-related factors contribute to remyelination failure after WMI, we sought accurate, cost-effective, and reproducible histopathological approaches for quantification of morphometric features of reactive astrogliosis in aged human white matter in patients with vascular brain injury (VBI). We compared 7 distinct approaches to quantify the features of glial fibrillary acidic protein (GFAP)-labeled astrocytes in the prefrontal white matter of brains from patients with VBI (n = 17, mean age 88.8 years) and controls that did not exhibit VBI (n = 11, mean age 86.6 years). Only modern stereological techniques (ie, optical fractionator and spaceballs) and virtual process thickness measurements demonstrated significant changes in astrocyte number, process length, or proximal process thickness in cases with VBI relative to controls. The widely employed methods of neuropathological scoring, antibody capture assay (histelide), area fraction fractionator, and Cavalieri point counting failed to detect significant differences in GFAP expression between the groups. Unbiased stereological approaches and virtual thickness measurements provided the only sensitive and accurate means to quantify astrocyte reactivity as a surrogate marker of WMI in human brains with VBI. PMID:27142644

  15. Comparison of the Relationship between Cerebral White Matter and Grey Matter in Normal Dogs and Dogs with Lateral Ventricular Enlargement.

    PubMed

    Schmidt, Martin J; Laubner, Steffi; Kolecka, Malgorzata; Failing, Klaus; Moritz, Andreas; Kramer, Martin; Ondreka, Nele

    2015-01-01

    Large cerebral ventricles are a frequent finding in brains of dogs with brachycephalic skull conformation, in comparison with mesaticephalic dogs. It remains unclear whether oversized ventricles represent a normal variant or a pathological condition in brachycephalic dogs. There is a distinct relationship between white matter and grey matter in the cerebrum of all eutherian mammals. The aim of this study was to determine if this physiological proportion between white matter and grey matter of the forebrain still exists in brachycephalic dogs with oversized ventricles. The relative cerebral grey matter, white matter and cerebrospinal fluid volume in dogs were determined based on magnetic-resonance-imaging datasets using graphical software. In an analysis of covariance (ANCOVA) using body mass as the covariate, the adjusted means of the brain tissue volumes of two groups of dogs were compared. Group 1 included 37 mesaticephalic dogs of different sizes with no apparent changes in brain morphology, and subjectively normal ventricle size. Group 2 included 35 brachycephalic dogs in which subjectively enlarged cerebral ventricles were noted as an incidental finding in their magnetic-resonance-imaging examination. Whereas no significant different adjusted means of the grey matter could be determined, the group of brachycephalic dogs had significantly larger adjusted means of lateral cerebral ventricles and significantly less adjusted means of relative white matter volume. This indicates that brachycephalic dogs with subjective ventriculomegaly have less white matter, as expected based on their body weight and cerebral volume. Our study suggests that ventriculomegaly in brachycephalic dogs is not a normal variant of ventricular volume. Based on the changes in the relative proportion of WM and CSF volume, and the unchanged GM proportions in dogs with ventriculomegaly, we rather suggest that distension of the lateral ventricles might be the underlying cause of pressure

  16. Comparison of the Relationship between Cerebral White Matter and Grey Matter in Normal Dogs and Dogs with Lateral Ventricular Enlargement

    PubMed Central

    Schmidt, Martin J.; Laubner, Steffi; Kolecka, Malgorzata; Failing, Klaus; Moritz, Andreas; Kramer, Martin; Ondreka, Nele

    2015-01-01

    Large cerebral ventricles are a frequent finding in brains of dogs with brachycephalic skull conformation, in comparison with mesaticephalic dogs. It remains unclear whether oversized ventricles represent a normal variant or a pathological condition in brachycephalic dogs. There is a distinct relationship between white matter and grey matter in the cerebrum of all eutherian mammals. The aim of this study was to determine if this physiological proportion between white matter and grey matter of the forebrain still exists in brachycephalic dogs with oversized ventricles. The relative cerebral grey matter, white matter and cerebrospinal fluid volume in dogs were determined based on magnetic-resonance-imaging datasets using graphical software. In an analysis of covariance (ANCOVA) using body mass as the covariate, the adjusted means of the brain tissue volumes of two groups of dogs were compared. Group 1 included 37 mesaticephalic dogs of different sizes with no apparent changes in brain morphology, and subjectively normal ventricle size. Group 2 included 35 brachycephalic dogs in which subjectively enlarged cerebral ventricles were noted as an incidental finding in their magnetic-resonance-imaging examination. Whereas no significant different adjusted means of the grey matter could be determined, the group of brachycephalic dogs had significantly larger adjusted means of lateral cerebral ventricles and significantly less adjusted means of relative white matter volume. This indicates that brachycephalic dogs with subjective ventriculomegaly have less white matter, as expected based on their body weight and cerebral volume. Our study suggests that ventriculomegaly in brachycephalic dogs is not a normal variant of ventricular volume. Based on the changes in the relative proportion of WM and CSF volume, and the unchanged GM proportions in dogs with ventriculomegaly, we rather suggest that distension of the lateral ventricles might be the underlying cause of pressure

  17. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease

    PubMed Central

    Joutel, Anne; Monet-Leprêtre, Marie; Gosele, Claudia; Baron-Menguy, Céline; Hammes, Annette; Schmidt, Sabine; Lemaire-Carrette, Barbara; Domenga, Valérie; Schedl, Andreas; Lacombe, Pierre; Hubner, Norbert

    2010-01-01

    Cerebral ischemic small vessel disease (SVD) is the leading cause of vascular dementia and a major contributor to stroke in humans. Dominant mutations in NOTCH3 cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic archetype of cerebral ischemic SVD. Progress toward understanding the pathogenesis of this disease and developing effective therapies has been hampered by the lack of a good animal model. Here, we report the development of a mouse model for CADASIL via the introduction of a CADASIL-causing Notch3 point mutation into a large P1-derived artificial chromosome (PAC). In vivo expression of the mutated PAC transgene in the mouse reproduced the endogenous Notch3 expression pattern and main pathological features of CADASIL, including Notch3 extracellular domain aggregates and granular osmiophilic material (GOM) deposits in brain vessels, progressive white matter damage, and reduced cerebral blood flow. Mutant mice displayed attenuated myogenic responses and reduced caliber of brain arteries as well as impaired cerebrovascular autoregulation and functional hyperemia. Further, we identified a substantial reduction of white matter capillary density. These neuropathological changes occurred in the absence of either histologically detectable alterations in cerebral artery structure or blood-brain barrier breakdown. These studies provide in vivo evidence for cerebrovascular dysfunction and microcirculatory failure as key contributors to hypoperfusion and white matter damage in this genetic model of ischemic SVD. PMID:20071773

  18. Intranasal Insulin Prevents Cognitive Decline, Cerebral Atrophy and White Matter Changes in Murine Type I Diabetic Encephalopathy

    ERIC Educational Resources Information Center

    Francis, George J.; Martinez, Jose A.; Liu, Wei Q.; Xu, Kevin; Ayer, Amit; Fine, Jared; Tuor, Ursula I.; Glazner, Gordon; Hanson, Leah R.; Frey, William H., II; Toth, Cory

    2008-01-01

    Insulin deficiency in type I diabetes may lead to cognitive impairment, cerebral atrophy and white matter abnormalities. We studied the impact of a novel delivery system using intranasal insulin (I-I) in a mouse model of type I diabetes (streptozotocin-induced) for direct targeting of pathological and cognitive deficits while avoiding potential…

  19. Outcome of cerebral arteriovenous malformations after linear accelerator reirradiation

    PubMed Central

    Moraes, Paulo L.; Dias, Rodrigo S.; Weltman, Eduardo; Giordani, Adelmo J.; Benabou, Salomon; Segreto, Helena R. C.; Segreto, Roberto A.

    2015-01-01

    Background: The aim of this study was to evaluate the clinical outcome of patients undergoing single-dose reirradiation using the Linear Accelerator (LINAC) for brain arteriovenous malformations (AVM). Methods: A retrospective study of 37 patients with brain AVM undergoing LINAC reirradiation between April 2003 and November 2011 was carried out. Patient characteristics, for example, gender, age, use of medications, and comorbidities; disease characteristics, for example, Spetzler–Martin grading system, location, volume, modified Pollock–Flickinger score; and treatment characteristics, for example, embolization, prescription dose, radiation dose–volume curves, and conformity index were analyzed. During the follow-up period, imaging studies were performed to evaluate changes after treatment and AVM cure. Complications, such as edema, rupture of the blood–brain barrier, and radionecrosis were classified as symptomatic and asymptomatic. Results: Twenty-seven patients underwent angiogram after reirradiation and the percentage of angiographic occlusion was 55.5%. In three patients without obliteration, AVM shrinkage made it possible to perform surgical resection with a 2/3 cure rate. A reduction in AVM nidus volume greater than 50% after the first procedure was shown to be the most important predictor of obliteration. Another factor associated with AVM cure was a prescription dose higher than 15.5 Gy in the first radiosurgery. Two patients had permanent neurologic deficits. Factors correlated with complications were the prescription dose and maximum dose in the first procedure. Conclusion: This study suggests that single-dose reirradiation is safe and feasible in partially occluded AVM. Reirradiation may not benefit candidates whose prescribed dose was lower than 15.5 Gy in the first procedure and initial AVM nidus volume did not decrease by more than 50% before reirradiation. PMID:26110078

  20. Cerebral White Matter Lesions and Affective Episodes Correlate in Male Individuals with Bipolar Disorder

    PubMed Central

    Birner, Armin; Seiler, Stephan; Lackner, Nina; Bengesser, Susanne A.; Queissner, Robert; Fellendorf, Frederike T.; Platzer, Martina; Ropele, Stefan; Enzinger, Christian; Schwingenschuh, Petra; Mangge, Harald; Pirpamer, Lukas; Deutschmann, Hannes; McIntyre, Roger S.; Kapfhammer, Hans-Peter; Reininghaus, Bernd; Reininghaus, Eva Z.

    2015-01-01

    Background Cerebral white matter lesions (WML) have been found in normal aging, vascular disease and several neuropsychiatric conditions. Correlations of WML with clinical parameters in BD have been described, but not with the number of affective episodes, illness duration, age of onset and Body Mass Index in a well characterized group of euthymic bipolar adults. Herein, we aimed to evaluate the associations between bipolar course of illness parameters and WML measured with volumetric analysis. Methods In a cross-sectional study 100 euthymic individuals with BD as well as 54 healthy controls (HC) were enrolled to undergo brain magnetic resonance imaging using 3T including a FLAIR sequence for volumetric assessment of WML-load using FSL-software. Additionally, clinical characteristics and psychometric measures including Structured Clinical Interview according to DSM-IV, Hamilton-Depression, Young Mania Rating Scale and Beck’s Depression Inventory were evaluated. Results Individuals with BD had significantly more (F = 3.968, p < .05) WML (Mdn = 3710mm3; IQR = 2961mm3) than HC (Mdn = 2185mm3; IQR = 1665mm3). BD men (Mdn = 4095mm3; IQR = 3295mm3) and BD women (Mdn = 3032mm3; IQR = 2816mm3) did not significantly differ as to the WML-load or the number and type of risk factors for WML. However, in men only, the number of manic/hypomanic episodes (r = 0.72; p < .001) as well as depressive episodes (r = 0.51; p < .001) correlated positively with WML-load. Conclusions WML-load strongly correlated with the number of manic episodes in male BD patients, suggesting that men might be more vulnerable to mania in the context of cerebral white matter changes. PMID:26252714

  1. Neuropathological investigation of cerebral white matter lesions caused by closed head injury.

    PubMed

    Onaya, Mitsumoto

    2002-12-01

    In order to ascertain whether there is widespread axonal disruption of cerebral white matter in the so-called 'diffuse axonal injury' (DAI), a type of closed head injury, proposed by Adams et al. the author investigated his own cases clinicopathologically. Twenty-six male autopsied cases of head injury, aged between 19 and 84, 15 of which had sustained road traffic accidents, were examined; the others were due to falling from heights and so on. The study group all belonged to non-missile head injuries and included 12 cases of diffuse brain injury, as well as 14 cases of focal brain injury, according to the classification of Gennarelli et al. The survival time ranged from 2 h to 21 years. Formalin-fixed brains were cut coronally so as to make paraffin-embedded hemispheric sections. Then these sections were stained conventionally (HE, Bodian, Kluver-Barrera and Holzer) and immunohistochemically (GFAP) to assess axonal decrease, myelin pallor and gliosis by the use of light microscopy. In the 13 chronic cases that died more than 1 month after the accidents, the intensities of gliosis, myelin pallor and axonal decrease tended to correlate with each other. In the 13 acute cases who died less than 1 month after their accident, the degree of axonal decrease in white matter seemed to correlate with the severity of myelin pallor. Regardless of types of trauma, however, axonal retraction balls, the so-called hallmark of DAI, were found only with myelin pallor suggesting the presence of brain swelling after the injury. Therefore these findings indicate that it may be difficult to accept the notion of DAI, that is, the presence of axonal retraction balls without brain swelling. In addition, diffuse vascular injury (2 cases) as well as rarefaction of subcortical white matter (6 cases) were presented and their pathogenesis individually discussed based on a literature review. PMID:12564763

  2. Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures

    PubMed Central

    Promjunyakul, N.; Lahna, D.; Kaye, J.A.; Dodge, H.H.; Erten-Lyons, D.; Rooney, W.D.; Silbert, L.C.

    2015-01-01

    Objective White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify ‘WM at risk’, or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up. Methods Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI. Results CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time. Conclusions A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences. PMID:26106546

  3. Cerebral gray and white matter changes and clinical course in metachromatic leukodystrophy

    PubMed Central

    í Dali, Christine; Clas, Philipp; Böhringer, Judith; Duno, Morten; Krarup, Christian; Kehrer, Christiane; Wilke, Marko; Krägeloh-Mann, Ingeborg

    2012-01-01

    Objective: Metachromatic leukodystrophy (MLD) is a rare metabolic disorder leading to demyelination and rapid neurologic deterioration. As therapeutic options evolve, it seems essential to understand and quantify progression of the natural disease. The aim of this study was to assess cerebral volumetric changes in children with MLD in comparison to normal controls and in relation to disease course. Method: Eighteen patients with late-infantile MLD and 42 typically developing children in the same age range (20–59 months) were analyzed in a cross-sectional study. Patients underwent detailed genetic, biochemical, electrophysiologic, and clinical characterization. Cerebral gray matter (GM) and white matter (WM) volumes were assessed by multispectral segmentation of T1- and T2-weighted MRI. In addition, the demyelinated WM (demyelination load) was automatically quantified in T2-weighted images of the patients, and analyzed in relation to the clinical course. Results: WM volumes of patients did not differ from controls, although their growth curves were slightly different. GM volumes of patients, however, were on average 10.7% (confidence interval 6.0%–14.9%, p < 0.001) below those of normally developing children. The demyelination load (corrected for total WM volume) increased with disease duration (p < 0.003) and motor deterioration (p < 0.001). Conclusion: GM volume in patients with MLD is reduced when compared with healthy controls, already at young age. This supports the notion that, beside demyelination, neuronal dysfunction caused by neuronal storage plays an additional role in the disease process. The demyelination load may be a useful noninvasive imaging marker for disease progression and may serve as reference for therapeutic intervention. PMID:22993277

  4. Cerebral Palsy

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Cerebral Palsy KidsHealth > For Kids > Cerebral Palsy Print A A ... the things that kids do every day. What's CP? Some kids with CP use wheelchairs and others ...

  5. DTI Study of Cerebral Normal-Appearing White Matter in Hereditary Neuropathy With Liability to Pressure Palsies (HNPP).

    PubMed

    Wang, Wei-Wei; Song, Chun-Li; Huang, Liang; Song, Qing-Wei; Liang, Zhan-Hua; Wei, Qiang; Hu, Jia-Ni; Miao, Yan-Wei; Wu, Bing; Xie, Lizhi

    2015-10-01

    The majority of previous studies on hereditary neuropathy with liability to pressure palsies (HNPP) were focused on peripheral nerves, whereas cerebral alterations in HNPP have been less attended to. In this work, Diffusion tensor imaging (DTI) was used to detect the changes in WM, especially in the normal-appearing white matter (NAWM) in HNPP patients for its sensitivity in probing the microstructure of WM, the sensitive metric was searched for probing cerebral alterations and the regional distribution of cerebral abnormalities was identified. Twelve HNPP patients and 12 age- and gender-matched healthy controls underwent the conventional MRI, DTI scan, and electrophysiological examination. The conventional MRI images were first analyzed to identify abnormal intense regions and the NAWM regions. NAWM refers to the white matter regions that do not include the lesions on conventional MRI. The apparent diffusion coefficient and fractional anisotropy (FA) values of the NAWM were then measured and compared between patient and control groups. The sensitivity and specificity of 3 methods and the cerebral regional distribution of MR signal abnormalities were further analyzed. Hyperintense foci were observed on T2 weighted image and fluid attenuated inversion recovery images in 6 patients. Compared to the controls, FA values of the patients were significantly lower in bilateral frontal, orbitofrontal, and temporal NAWMs; whereas the electrophysiological examination results of patients and controls exhibited no statistically significant difference. The sensitivity of FA value was higher than that of electrophysiological examination and conventional MRI. The majority of abnormal signals on conventional MRI images and abnormal FA values were located in the frontal and temporal lobes. The results of our study show cerebral WM changes in HNPP patients. FA value in DTI has been shown to be sensitive to the cerebral microstructural changes in HNPP. The frontal lobe is the

  6. Genome-wide meta-analysis of cerebral white matter hyperintensities in patients with stroke

    PubMed Central

    Zhang, Cathy R.; Adib-Samii, Poneh; Devan, William J.; Parsons, Owen E.; Lanfranconi, Silvia; Gregory, Sarah; Cloonan, Lisa; Falcone, Guido J.; Radmanesh, Farid; Fitzpatrick, Kaitlin; Kanakis, Allison; Barrick, Thomas R.; Moynihan, Barry; Lewis, Cathryn M.; Boncoraglio, Giorgio B.; Lemmens, Robin; Thijs, Vincent; Sudlow, Cathie; Wardlaw, Joanna; Rothwell, Peter M.; Meschia, James F.; Worrall, Bradford B.; Levi, Christopher; Bevan, Steve; Furie, Karen L.; Dichgans, Martin; Rosand, Jonathan; Markus, Hugh S.; Rost, Natalia

    2016-01-01

    Objective: For 3,670 stroke patients from the United Kingdom, United States, Australia, Belgium, and Italy, we performed a genome-wide meta-analysis of white matter hyperintensity volumes (WMHV) on data imputed to the 1000 Genomes reference dataset to provide insights into disease mechanisms. Methods: We first sought to identify genetic associations with white matter hyperintensities in a stroke population, and then examined whether genetic loci previously linked to WMHV in community populations are also associated in stroke patients. Having established that genetic associations are shared between the 2 populations, we performed a meta-analysis testing which associations with WMHV in stroke-free populations are associated overall when combined with stroke populations. Results: There were no associations at genome-wide significance with WMHV in stroke patients. All previously reported genome-wide significant associations with WMHV in community populations shared direction of effect in stroke patients. In a meta-analysis of the genome-wide significant and suggestive loci (p < 5 × 10−6) from community populations (15 single nucleotide polymorphisms in total) and from stroke patients, 6 independent loci were associated with WMHV in both populations. Four of these are novel associations at the genome-wide level (rs72934505 [NBEAL1], p = 2.2 × 10−8; rs941898 [EVL], p = 4.0 × 10−8; rs962888 [C1QL1], p = 1.1 × 10−8; rs9515201 [COL4A2], p = 6.9 × 10−9). Conclusions: Genetic associations with WMHV are shared in otherwise healthy individuals and patients with stroke, indicating common genetic susceptibility in cerebral small vessel disease. PMID:26674333

  7. Cilostazol reduces blood brain barrier dysfunction, white matter lesion formation and motor deficits following chronic cerebral hypoperfusion.

    PubMed

    Edrissi, Hamidreza; Schock, Sarah C; Cadonic, Robert; Hakim, Antoine M; Thompson, Charlie S

    2016-09-01

    Cerebral small vessel disease (CSVD) is a pathological process leading to lacunar infarcts, leukoaraiosis and cerebral microbleeds. Dysfunction of the blood brain barrier (BBB) has been proposed as a mechanism in the progression cerebral small vessel disease. A rodent model commonly used to study some aspects of CSVD is bilateral common carotid artery occlusion (BCCAO) in the rat. In the present study it was determined that gait impairment, as determined by a tapered beam test, and BBB permeability increased following BCCAO. Cilostazol, a type III phosphodiesterase inhibitor, has been shown to have anti-apoptotic effects and prevent white matter vacuolation and rarefaction induced by BCCAO in rats. In this study the protective effect of cilostazol administration on the increase BBB permeability following BCCAO was determined as well as the effect on plasma levels of circulating microparticles (MPs), cerebral white matter rarefaction, glial activation and gait disturbance. The effect of cilostazol on in vitro endothelial barriers was also evaluated. Cilostazol treatment improved BBB permeability and reduced gait disturbance, visual impairment and microglial activation in optic tract following BCCAO in vivo. It also reduced the degree of cell death and the reduction in trans-endothelial electrical resistance (TEER) in artificial endothelial barriers in vitro induced by MP treatment of in vitro barriers. PMID:27350079

  8. APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume.

    PubMed

    Freedman, Barry I; Gadegbeku, Crystal A; Bryan, R Nick; Palmer, Nicholette D; Hicks, Pamela J; Ma, Lijun; Rocco, Michael V; Smith, S Carrie; Xu, Jianzhao; Whitlow, Christopher T; Wagner, Benjamin C; Langefeld, Carl D; Hawfield, Amret T; Bates, Jeffrey T; Lerner, Alan J; Raj, Dominic S; Sadaghiani, Mohammad S; Toto, Robert D; Wright, Jackson T; Bowden, Donald W; Williamson, Jeff D; Sink, Kaycee M; Maldjian, Joseph A; Pajewski, Nicholas M; Divers, Jasmin

    2016-08-01

    To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (β = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (β = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (β= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (β/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease. PMID:27342958

  9. Prenatal ischemia deteriorates white matter, brain organization, and function: implications for prematurity and cerebral palsy.

    PubMed

    Coq, Jacques-Olivier; Delcour, Maxime; Massicotte, Vicky S; Baud, Olivier; Barbe, Mary F

    2016-03-01

    Cerebral palsy (CP) describes a group of neurodevelopmental disorders of posture and movement that are frequently associated with sensory, behavioral, and cognitive impairments. The clinical picture of CP has changed with improved neonatal care over the past few decades, resulting in higher survival rates of infants born very preterm. Children born preterm seem particularly vulnerable to perinatal hypoxia-ischemia insults at birth. Animal models of CP are crucial for elucidating underlying mechanisms and for development of strategies of neuroprotection and remediation. Most animal models of CP are based on hypoxia-ischemia around the time of birth. In this review, we focus on alterations of brain organization and functions, especially sensorimotor changes, induced by prenatal ischemia in rodents and rabbits, and relate these alterations to neurodevelopmental disorders found in preterm children. We also discuss recent literature that addresses the relationship between neural and myelin plasticity, as well as possible contributions of white matter injury to the emergence of brain dysfunctions induced by prenatal ischemia. PMID:27027601

  10. Heritability and genetic correlation between the cerebral cortex and associated white matter connections.

    PubMed

    Shen, Kai-Kai; Doré, Vincent; Rose, Stephen; Fripp, Jurgen; McMahon, Katie L; de Zubicaray, Greig I; Martin, Nicholas G; Thompson, Paul M; Wright, Margaret J; Salvado, Olivier

    2016-06-01

    The aim of this study is to investigate the genetic influence on the cerebral cortex, based on the analyses of heritability and genetic correlation between grey matter (GM) thickness, derived from structural MR images (sMRI), and associated white matter (WM) connections obtained from diffusion MRI (dMRI). We measured on sMRI the cortical thickness (CT) from a large twin imaging cohort using a surface-based approach (N = 308, average age 22.8 ± 2.3 SD). An ACE model was employed to compute the heritability of CT. WM connections were estimated based on probabilistic tractography using fiber orientation distributions (FOD) from dMRI. We then fitted the ACE model to estimate the heritability of CT and FOD peak measures along WM fiber tracts. The WM fiber tracts where genetic influence was detected were mapped onto the cortical surface. Bivariate genetic modeling was performed to estimate the cross-trait genetic correlation between the CT and the FOD-based connectivity of the tracts associated with the cortical regions. We found some cortical regions displaying heritable and genetically correlated GM thickness and WM connectivity, forming networks under stronger genetic influence. Significant heritability and genetic correlations between the CT and WM connectivity were found in regions including the right postcentral gyrus, left posterior cingulate gyrus, right middle temporal gyri, suggesting common genetic factors influencing both GM and WM. Hum Brain Mapp 37:2331-2347, 2016. © 2016 Wiley Periodicals, Inc. PMID:27006297

  11. Cerebral blood flow velocity and cranial fluid volume decrease during +Gz acceleration

    NASA Technical Reports Server (NTRS)

    Kawai, Y.; Puma, S. C.; Hargens, A. R.; Murthy, G.; Warkander, D.; Lundgren, C. E.

    1997-01-01

    Cerebral blood flow (CBF) velocity and cranial fluid volume, which is defined as the total volume of intra- and extracranial fluid, were measured using transcranial Doppler ultrasonography and rheoencephalography, respectively, in humans during graded increase of +Gz acceleration (onset rate: 0.1 G/s) without straining maneuvers. Gz acceleration was terminated when subjects' vision decreased to an angle of less than or equal to 60 degrees, which was defined as the physiological end point. In five subjects, mean CBF velocity decreased 48% from a baseline value of 59.4 +/- 11.2 cm/s to 31.0 +/- 5.6 cm/s (p<0.01) with initial loss of peripheral vision at 5.7 +/- 0.9 Gz. On the other hand, systolic CBF velocity did not change significantly during increasing +Gz acceleration. Cranial impedance, which is proportional to loss of cranial fluid volume, increased by 2.0 +/- 0.8% above the baseline value at the physiological end point (p<0.05). Both the decrease of CBF velocity and the increase of cranial impedance correlated significantly with Gz. These results suggest that +Gz acceleration without straining maneuvers decreases CBF velocity to half normal and probably causes a caudal fluid shift from both intra- and extracranial tissues.

  12. Children with New Onset Epilepsy Exhibit Diffusion Abnormalities in Cerebral White Matter in the Absence of Volumetric Differences

    PubMed Central

    Hutchinson, Elizabeth; Pulsipher, Dalin; Dabbs, Kevin; Myers y Gutierrez, Adan; Sheth, Raj; Jones, Jana; Seidenberg, Michael; Meyerand, Elizabeth; Hermann, Bruce

    2010-01-01

    SUMMARY The purpose of this investigation was to examine the diffusion properties of cerebral white matter in children with recent onset epilepsy (n=19) compared to healthy controls (n=11). Subjects underwent DTI with quantification of mean diffusion (MD), fractional anisotropy (FA), axial diffusivity (Dax) and radial diffusivity (Drad) for regions of interest including anterior and posterior corpus callosum, fornix, cingulum, and internal and external capsules. Quantitative volumetrics were also performed for the corpus callosum and its subregions (anterior, midbody and posterior) and total lobar white and gray matter for the frontal, parietal, temporal and occipital lobes. The results demonstrated no group differences in total lobar gray or white matter volumes or volume of the corpus callosum and its subregions, but did show reduced FA and increased Drad in the posterior corpus callosum and cingulum. These results provide the earliest indication of microstructural abnormality in cerebral white matter among children with idiopathic epilepsies. This abnormality occurs in the context of normal volumetrics and suggests disruption in myelination processes. PMID:20044239

  13. Multi-Ethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI

    PubMed Central

    Verhaaren, Benjamin F.J.; Debette, Stéphanie; Bis, Joshua C.; Smith, Jennifer A.; Ikram, M. Kamran; Adams, Hieab H.; Beecham, Ashley H.; Rajan, Kumar B.; Lopez, Lorna M.; Barral, Sandra; van Buchem, Mark A.; van der Grond, Jeroen; Smith, Albert V.; Hegenscheid, Katrin; Aggarwal, Neelum T.; de Andrade, Mariza; Atkinson, Elizabeth J.; Beekman, Marian; Beiser, Alexa S.; Blanton, Susan H.; Boerwinkle, Eric; Brickman, Adam M.; Bryan, R. Nick; Chauhan, Ganesh; Chen, Christopher P.L.H.; Chouraki, Vincent; de Craen, Anton J.M.; Crivello, Fabrice; Deary, Ian J.; Deelen, Joris; De Jager, Philip L.; Dufouil, Carole; Elkind, Mitchell S.V.; Evans, Denis A.; Freudenberger, Paul; Gottesman, Rebecca F.; Guðnason, Vilmundur; Habes, Mohamad; Heckbert, Susan R.; Heiss, Gerardo; Hilal, Saima; Hofer, Edith; Hofman, Albert; Ibrahim-Verbaas, Carla A.; Knopman, David S.; Lewis, Cora E.; Liao, Jiemin; Liewald, David C.M.; Luciano, Michelle; van der Lugt, Aad; Martinez, Oliver O.; Mayeux, Richard; Mazoyer, Bernard; Nalls, Mike; Nauck, Matthias; Niessen, Wiro J.; Oostra, Ben A.; Psaty, Bruce M.; Rice, Kenneth M.; Rotter, Jerome I.; von Sarnowski, Bettina; Schmidt, Helena; Schreiner, Pamela J.; Schuur, Maaike; Sidney, Stephen S.; Sigurdsson, Sigurdur; Slagboom, P. Eline; Stott, David J.M.; van Swieten, John C.; Teumer, Alexander; Töglhofer, Anna Maria; Traylor, Matthew; Trompet, Stella; Turner, Stephen T.; Tzourio, Christophe; Uh, Hae-Won; Uitterlinden, André G.; Vernooij, Meike W.; Wang, Jing J.; Wong, Tien Y.; Wardlaw, Joanna M.; Windham, B. Gwen; Wittfeld, Katharina; Wolf, Christiane; Wright, Clinton B.; Yang, Qiong; Zhao, Wei; Zijdenbos, Alex; Jukema, J. Wouter; Sacco, Ralph L.; Kardia, Sharon L.R.; Amouyel, Philippe; Mosley, Thomas H.; Longstreth, W. T.; DeCarli, Charles C.; van Duijn, Cornelia M.; Schmidt, Reinhold; Launer, Lenore J.; Grabe, Hans J.; Seshadri, Sudha S.; Ikram, M. Arfan; Fornage, Myriam

    2015-01-01

    Background The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multi-ethnic genome-wide association studies. Methods and Results We included 21,079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (N=17,936), African (N=1,943), Hispanic (N=795), and Asian (N=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each SNP and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (p=2.7×10−19) and identified novel loci on chr10q24 (p=1.6×10−9) and chr2p21 (p=4.4×10−8). In the multi-ethnic meta-analysis, we identified two additional loci, on chr1q22 (p=2.0×10−8) and chr2p16 (p=1.5×10−8). The novel loci contained genes that have been implicated in Alzheimer’s disease (chr2p21, chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24, chr2p16). Conclusions We identified four novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of white matter hyperintensities in addition to previously-proposed ischemic mechanisms. PMID:25663218

  14. In vivo study of cerebral white matter in the dog using diffusion tensor tractography.

    PubMed

    Anaya García, Mitzi Sarahí; Hernández Anaya, Jael Sarahí; Marrufo Meléndez, Oscar; Velázquez Ramírez, José Luis; Palacios Aguiar, Ricardo

    2015-01-01

    Conventional magnetic resonance imaging (MRI) allows investigators and clinicians to observe the anatomy and injuries of the cerebral white matter (CWM) in dogs. However, dynamic images based on the diffusion tensor (DT) technique are required to assess fiber tract integrity of the CWM. Diffusion tensor tractography (DTT) produces a three-dimensional representation in which data are displayed on a colored map obtained from the anisotropy of water molecules in the CWM tracts. Fractional anisotropy (FA) is a value that measures changes in water diffusion, which can occur if the CWM tracts are displaced, disrupted, or infiltrated. The goal of this study was to determine the feasibility of DTT for in vivo examination of the normal appearance of CWM in dogs through visual and quantitative analysis of the most representative CWM tracts. Nine tractographies were performed on healthy dogs using a 3T MRI scanner. T1- and T2-weighted images and DTI were acquired at different planes. Using DTT, three-dimensional reconstructions were obtained. Fractional ansisotropy and apparent diffusion coefficient (ADC) values of the right and left corticospinal tracts, corpus callosum, cingulum, and right and left fronto-occipital fasciculus were determined. Tract reconstructions were similar in 8/9 healthy dogs. Values for FA and ADC were similar in all the dogs. In one dog, tract reconstructions were inhomogeneous; these were displaced because it had larger lateral ventricles. Findings indicated that DTT is a feasible technique for in vivo study of CWM in dogs and that it complements information from conventional MRI. PMID:25288360

  15. IN VIVO STUDY OF CEREBRAL WHITE MATTER IN THE DOG USING DIFFUSION TENSOR TRACTOGRAPHY

    PubMed Central

    Anaya García, Mitzi Sarahí; Hernández Anaya, Jael Sarahí; Marrufo Meléndez, Oscar; Velázquez Ramírez, José Luis; Palacios Aguiar, Ricardo

    2015-01-01

    Conventional magnetic resonance imaging (MRI) allows investigators and clinicians to observe the anatomy and injuries of the cerebral white matter (CWM) in dogs. However, dynamic images based on the diffusion tensor (DT) technique are required to assess fiber tract integrity of the CWM. Diffusion tensor tractography (DTT) produces a three-dimensional representation in which data are displayed on a colored map obtained from the anisotropy of water molecules in the CWM tracts. Fractional anisotropy (FA) is a value that measures changes in water diffusion, which can occur if the CWM tracts are displaced, disrupted, or infiltrated. The goal of this study was to determine the feasibility of DTT for in vivo examination of the normal appearance of CWM in dogs through visual and quantitative analysis of the most representative CWM tracts. Nine tractographies were performed on healthy dogs using a 3T MRI scanner. T1- and T2-weighted images and DTI were acquired at different planes. Using DTT, three-dimensional reconstructions were obtained. Fractional ansisotropy and apparent diffusion coefficient (ADC) values of the right and left corticospinal tracts, corpus callosum, cingulum, and right and left fronto-occipital fasciculus were determined. Tract reconstructions were similar in 8/9 healthy dogs. Values for FA and ADC were similar in all the dogs. In one dog, tract reconstructions were inhomogeneous; these were displaced because it had larger lateral ventricles. Findings indicated that DTT is a feasible technique for in vivo study of CWM in dogs and that it complements information from conventional MRI. PMID:25288360

  16. Thalamic fractional anisotropy predicts accrual of cerebral white matter damage in older subjects with small-vessel disease

    PubMed Central

    Cavallari, Michele; Moscufo, Nicola; Meier, Dominik; Skudlarski, Pawel; Pearlson, Godfrey D; White, William B; Wolfson, Leslie; Guttmann, Charles RG

    2014-01-01

    White matter hyperintensities (WMHs) and lacunes are magnetic resonance imaging hallmarks of cerebral small-vessel disease, which increase the risk of stroke, cognitive, and mobility impairment. Although most studies of cerebral small-vessel disease have focused on white matter abnormalities, the gray matter (GM) is also affected, as evidenced by frequently observed lacunes in subcortical GM. Diffusion tensor imaging (DTI) is sensitive to subtle neurodegenerative changes in deep GM structures. We explored the relationship between baseline DTI characteristics of the thalamus, caudate, and putamen, and the volume and subsequent accrual of WMHs over a 4-year period in 56 community-dwelling older (⩾75 years) individuals. Baseline thalamic fractional anisotropy (FA) was an independent predictor of WMH accrual. WMH accrual also correlated with baseline lacune count and baseline WMH volume, the latter showing the strongest predictive power, explaining 27.3% of the variance. The addition of baseline thalamic FA in multivariate modeling increased this value by 70%, which explains 46.5% of the variance in WMH accrual rate. Thalamic FA might serve as a novel predictor of cerebral small-vessel disease progression in clinical settings and trials. Furthermore, our findings point to the possibility of a causal relationship between thalamic damage and the accrual of WMHs. PMID:24824915

  17. Effects of statins on the progression of cerebral white matter lesion: Post hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study.

    PubMed

    Mok, Vincent C T; Lam, Wynnie W M; Fan, Yu Hua; Wong, Adrian; Ng, Ping Wing; Tsoi, Tak Hon; Yeung, Vincent; Wong, Ka Sing

    2009-05-01

    Arteriosclerotic related cerebral white matter lesion (WML) is associated with increased risk of death, stroke, dementia, depression, gait disturbance, and urinary incontinence. We investigated the effects of statins on WML progression by performing a post hoc analysis on the ROCAS (Regression of Cerebral Artery Stenosis) study, which is a randomized, double-blind, placebo-controlled study evaluating the effects of statins upon asymptomatic middle cerebral artery stenosis progression among stroke-free individuals. Two hundreds and eight randomized subjects were assigned to either placebo (n = 102) or simvastatin 20 mg daily (n = 106) for 2 years. Baseline severity of WML was graded visually into none, mild, and severe. Volume (cm3) of WML was determined quantitatively at baseline and at end of study using a semi-automated method based on MRI. Primary outcome was the change in WML volume over 2 years. After 2 years of follow-up, there was no significant change in WML volume between the active and the placebo group as a whole. However, stratified analysis showed that for those with severe WML at baseline, the median volume increase in the active group (1.9 cm3) was less compared with that in the placebo group (3.0 cm3; P = 0.047). Linear multivariate regression analysis identified that baseline WML volume (beta = 0.63, P < 0.001) and simvastatin treatment (beta = -0.214, P = 0.043) independently predicted change in WML volume. Our findings suggest that statins may delay the progression of cerebral WML only among those who already have severe WML at baseline. PMID:19252811

  18. Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism.

    PubMed

    Trangmar, Steven J; Chiesa, Scott T; Llodio, Iñaki; Garcia, Benjamin; Kalsi, Kameljit K; Secher, Niels H; González-Alonso, José

    2015-11-01

    Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, whereas the cerebral metabolic rate for O2 (CMRO2 ) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, 10 male cyclists cycled in the heat for ∼2 h with (control) and without fluid replacement (dehydration) while internal and external carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate CMRO2 . In study 2, in 8 male subjects, middle cerebral artery blood velocity was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, internal carotid artery flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced O2 and glucose extraction (P < 0.05). External carotid artery flow increased for 1 h but declined before exhaustion. Fluid ingestion maintained cerebral and extracranial perfusion throughout nonfatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat, dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extracranial perfusion. Thus, fatigue is related to a reduction in CBF and extracranial perfusion rather than CMRO2 . PMID:26371170

  19. Accelerated life test for high-power white LED based on spectroradiometric measurement

    NASA Astrophysics Data System (ADS)

    Shen, Haiping; Pan, Jiangen; Feng, Huajun

    2008-03-01

    We implement an accelerated life test for the high-power white LEDs based on spectroradiometric measurement. The luminous flux degradation performances are investigated at both the rated current of 350mA and a higher current of 500mA. The average lifetime of the LEDs is 7057 hours at 350mA and 3508 hours at 500mA. The variations of the color of the white LEDs are studied. The color of the low quality white LEDs changes greatly, while the high quality white LEDs keep their color stable. The degradation performances of the chip and phosphor are studied separately. The quantum efficiency of the phosphor becomes lower from 350mA to 500mA current supply. The LED chip degrades faster than the phosphor during the 500mA high current aging. The luminous flux increase and the peak wavelength shift from 350mA to 500mA current supply are found to be useful lifetime indicating parameters that correlate well to the reliability of the high-power white LEDs.

  20. Consistent Injury to Medium Spiny Neurons and White Matter in the Mouse Striatum after Prolonged Transient Global Cerebral Ischemia

    PubMed Central

    Yoshioka, Hideyuki; Niizuma, Kuniyasu; Katsu, Masataka; Sakata, Hiroyuki; Okami, Nobuya

    2011-01-01

    Abstract A reproducible transient global cerebral ischemia (tGCI) mouse model has not been fully established. Although striatal neurons and white matter are recognized to be vulnerable to ischemia, their injury after tGCI in mice has not been elucidated. The purpose of this study was to evaluate injuries to striatal neurons and white matter after tGCI in C57BL/6 mice, and to develop a reproducible tGCI model. Male C57BL/6 mice were subjected to tGCI by bilateral common carotid artery occlusion (BCCAO). Mice whose cortical cerebral blood flow after BCCAO decreased to less than 13% of the pre-ischemic value were used. Histological analysis showed that at 3 days after 22 min of BCCAO, striatal neurons were injured more consistently than those in other brain regions. Quantitative analysis of cytochrome c release into the cytosol and DNA fragmentation in the striatum showed consistent injury to the striatum. Immunohistochemistry and Western blot analysis revealed that DARPP-32-positive medium spiny neurons, the majority of striatal neurons, were the most vulnerable among the striatal neuronal subpopulations. The striatum (especially medium spiny neurons) was susceptible to oxidative stress after tGCI, which is probably one of the mechanisms of vulnerability. SMI-32 immunostaining showed that white matter in the striatum was also consistently injured 3 days after 22 min of BCCAO. We thus suggest that this is a tGCI model using C57BL/6 mice that consistently produces neuronal and white matter injury in the striatum by a simple technique. This model can be highly applicable for elucidating molecular mechanisms in the brain after global ischemia. PMID:21309724

  1. Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns

    PubMed Central

    Logan, J. Wells; O’Shea, T. Michael; Allred, Elizabeth N.; Laughon, Matthew M.; Bose, Carl L.; Dammann, Olaf; Batton, Daniel G.; Kuban, Karl C.; Paneth, Nigel; Leviton, Alan

    2011-01-01

    Objectives To evaluate, in extremely low gestational age newborns (ELGANs), relationships between indicators of early postnatal hypotension and cranial ultrasound indicators of cerebral white matter damage imaged in the nursery and cerebral palsy diagnoses at 24 month follow-up. Methods The 1041 infants in this prospective study were born at < 28 weeks gestation, were assessed for 3 indicators of hypotension in the first 24 postnatal hours, had at least one set of protocol cranial ultrasound scans, and were evaluated with a structured neurologic exam at 24 months corrected age. Indicators of hypotension included: 1) lowest mean arterial pressure (MAP) in the lowest quartile for gestational age; 2) treatment with a vasopressor; and 3) blood pressure lability, defined as the upper quartile of the difference between each infant’s lowest and highest MAP. Outcomes included indicators of cerebral white matter damage, i.e. moderate/severe ventriculomegaly or an echolucent lesion on cranial ultrasound, and cerebral palsy diagnoses at 24 months gestation. Logistic regression was used to evaluate relationships among hypotension indicators and outcomes, adjusting for potential confounders. Results Twenty-one percent of surviving infants had a lowest blood pressure in the lowest quartile for gestational age, 24% were treated with vasopressors, and 24% had labile blood pressure. Among infants with these hypotension indicators, 10% percent developed ventriculomegaly and 7% developed an echolucent lesion. At 24-months follow-up, 6% had developed quadriparesis, 4% diparesis, and 2% hemiparesis. After adjusting for confounders, we found no association between indicators of hypotension, and indicators of cerebral white matter damage or a cerebral palsy diagnosis. Conclusions The absence of an association between indicators of hypotension and cerebral white matter damage and or cerebral palsy suggests that early hypotension may not be important in the pathogenesis of brain injury

  2. Immediate remote ischemic postconditioning after hypoxia ischemia in piglets protects cerebral white matter but not grey matter

    PubMed Central

    Ezzati, Mojgan; Bainbridge, Alan; Broad, Kevin D; Kawano, Go; Oliver-Taylor, Aaron; Rocha-Ferreira, Eridan; Alonso-Alconada, Daniel; Fierens, Igor; Rostami, Jamshid; Jane Hassell, K; Tachtsidis, Ilias; Gressens, Pierre; Hristova, Mariya; Bennett, Kate; Lebon, Sophie; Fleiss, Bobbi; Yellon, Derek; Hausenloy, Derek J; Golay, Xavier

    2015-01-01

    Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. Our aim was to assess whether RIPostC is protective following cerebral hypoxia-ischemia in a piglet model of neonatal encephalopathy (NE) using magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry. After hypoxia-ischemia (HI), 16 Large White female newborn piglets were randomized to: (i) no intervention (n = 8); (ii) RIPostC – with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (n = 8). RIPostC reduced the hypoxic-ischemic-induced increase in white matter proton MRS lactate/N acetyl aspartate (p = 0.005) and increased whole brain phosphorus-31 MRS ATP (p = 0.039) over the 48 h after HI. Cell death was reduced with RIPostC in the periventricular white matter (p = 0.03), internal capsule (p = 0.002) and corpus callosum (p = 0.021); there was reduced microglial activation in corpus callosum (p = 0.001) and more surviving oligodendrocytes in corpus callosum (p = 0.029) and periventricular white matter (p = 0.001). Changes in gene expression were detected in the white matter at 48 h, including KATP channel and endothelin A receptor. Immediate RIPostC is a potentially safe and promising brain protective therapy for babies with NE with protection in white but not grey matter. PMID:26661194

  3. Tigroid pattern of cerebral white matter involvement in chromosome 6p25 deletion syndrome with concomitant 5p15 duplication

    PubMed Central

    Balasubramanian, Meena; Smith, Kath; Williams, Steve; Griffiths, Paul D.; Parker, Michael J.; Mordekar, Santosh R.

    2012-01-01

    Sub-telomeric deletions of the short arm of chromosome 6 are a well-described clinical entity characterized by developmental impairment, hypotonia, eye abnormalities and defects in the heart and kidneys. Chromosome 5p terminal duplication is a rarer entity, associated with developmental impairment and facial dysmorphism. We report a 3-year-old patient with a chromosome 6p25.1pter deletion and chromosome 5p15.1pter duplication who had global developmental impairment and unusual cerebral white matter changes, with hypoplastic corpus callosum and cerebellar vermis on magnetic resonance imaging -brain scan. We discuss the differential diagnosis to consider in patients with this appearance on magnetic resonance imaging -brain scan and reiterate the need for chromosome analysis in patients with this pattern of developmental anomaly. Tigroid pattern of cerebral white matter involvement has not been reported in chromosomal deletion/duplication syndromes. With the increasing use of molecular karyotyping for patients with multiple congenital anomalies and developmental delay, it is important to consider the exact size and nature of chromosomal deletion/duplication, in order to provide families with prognostic information and recurrence risk. This in turn, will help provide valuable information regarding the natural history of rare chromosomal imbalances.

  4. DTI of the Visual Pathway - White Matter Tracts and Cerebral Lesions

    PubMed Central

    Hana, Ardian; Husch, Andreas; Gunness, Vimal Raj Nitish; Berthold, Christophe; Hana, Anisa; Dooms, Georges; Boecher Schwarz, Hans; Hertel, Frank

    2014-01-01

    DTI is a technique that identifies white matter tracts (WMT) non-invasively in healthy and non-healthy patients using diffusion measurements. Similar to visual pathways (VP), WMT are not visible with classical MRI or intra-operatively with microscope. DTI will help neurosurgeons to prevent destruction of the VP while removing lesions adjacent to this WMT. We have performed DTI on fifty patients before and after surgery between March 2012 to January 2014. To navigate we used a 3DT1-weighted sequence. Additionally, we performed a T2-weighted and DTI-sequences. The parameters used were, FOV: 200 x 200 mm, slice thickness: 2 mm, and acquisition matrix: 96 x 96 yielding nearly isotropic voxels of 2 x 2 x 2 mm. Axial MRI was carried out using a 32 gradient direction and one b0-image. We used Echo-Planar-Imaging (EPI) and ASSET parallel imaging with an acceleration factor of 2 and b-value of 800 s/mm². The scanning time was less than 9 min. The DTI-data obtained were processed using a FDA approved surgical navigation system program which uses a straightforward fiber-tracking approach known as fiber assignment by continuous tracking (FACT). This is based on the propagation of lines between regions of interest (ROI) which is defined by a physician. A maximum angle of 50, FA start value of 0.10 and ADC stop value of 0.20 mm²/s were the parameters used for tractography. There are some limitations to this technique. The limited acquisition time frame enforces trade-offs in the image quality. Another important point not to be neglected is the brain shift during surgery. As for the latter intra-operative MRI might be helpful. Furthermore the risk of false positive or false negative tracts needs to be taken into account which might compromise the final results. PMID:25226557

  5. Hypoxia during pregnancy in rats leads to the changes of the cerebral white matter in adult offspring

    SciTech Connect

    Wang, Lingxing; Cai, Ruowei; Lv, Guorong; Huang, Ziyang; Wang, Zhenhua

    2010-05-28

    The aim of the present study is to evaluate the effect of reduced fetal oxygen supply on cerebral white matter in the adult offspring and further assess its susceptibility to postnatal hypoxia and high-fat diet. Based on a 3 x 2 full factorial design consisting of three factors of maternal hypoxia, postnatal high-fat diet, and postnatal hypoxia, the ultrastructure of myelin, axon and capillaries were observed, and the expression of myelin basic protein (MBP), neurofilament-H+L(NF-H+L), and glial fibrillary acidic protein (GFAP) was analyzed in periventricular white matter of 16-month-old offspring. Demyelination, injured axon and damaged microvasculars were observed in maternal hypoxia offspring. The main effect of maternal hypoxia lead to decreased expression of MBP or NF-H+L, and increased expression of GFAP (all P < 0.05). Moreover, there was positive three-way interaction among maternal hypoxia, high-fat diet and postnatal hypoxia on MBP, NF-H+L or GFAP expression (all P < 0.05). In summary, our results indicated that maternal hypoxia during pregnancy in rats lead to changes of periventricular white matter in adult offspring, including demyelination, damaged axon and proliferated astroglia. This effect was amplified by high-fat diet and postnatal hypoxia.

  6. Sex-Dependent Influences of Obesity on Cerebral White Matter Investigated by Diffusion-Tensor Imaging

    PubMed Central

    Horstmann, Annette; Lepsien, Jöran; Busse, Franziska; Mohammadi, Siawoosh; Schroeter, Matthias L.; Stumvoll, Michael; Villringer, Arno; Pleger, Burkhard

    2011-01-01

    Several studies have shown that obesity is associated with changes in human brain function and structure. Since women are more susceptible to obesity than men, it seems plausible that neural correlates may also be different. However, this has not been demonstrated so far. To address this issue, we systematically investigated the brain's white matter (WM) structure in 23 lean to obese women (mean age 25.5 y, std 5.1 y; mean body mass index (BMI) 29.5 kg/m2, std 7.3 kg/m2) and 26 lean to obese men (mean age 27.1 y, std 5.0 y; mean BMI 28.8 kg/m2, std 6.8 kg/m2) with diffusion-weighted magnetic resonance imaging (MRI). There was no significant age (p>0.2) or BMI (p>0.7) difference between female and male participants. Using tract-based spatial statistics, we correlated several diffusion parameters including the apparent diffusion coefficient, fractional anisotropy (FA), as well as axial (λ∥) and radial diffusivity (λ⊥) with BMI and serum leptin levels. In female and male subjects, the putative axon marker λ∥ was consistently reduced throughout the corpus callosum, particularly in the splenium (r = −0.62, p<0.005). This suggests that obesity may be associated with axonal degeneration. Only in women, the putative myelin marker λ⊥ significantly increased with increasing BMI (r = 0.57, p<0.005) and serum leptin levels (r = 0.62, p<0.005) predominantly in the genu of the corpus callosum, suggesting additional myelin degeneration. Comparable structural changes were reported for the aging brain, which may point to accelerated aging of WM structure in obese subjects. In conclusion, we demonstrate structural WM changes related to an elevated body weight, but with differences between men and women. Future studies on obesity-related functional and structural brain changes should therefore account for sex-related differences. PMID:21494606

  7. Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity.

    PubMed

    Anthony Jalin, Angela M A; Lee, Jae-Chul; Cho, Geum-Sil; Kim, Chunsook; Ju, Chung; Pahk, Kisoo; Song, Hwa Young; Kim, Won-Ki

    2015-11-01

    Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusion-evoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-1β in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-κB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IκB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions. PMID:26535078

  8. Radiation-Induced Changes in Normal-Appearing White Matter in Patients With Cerebral Tumors: A Diffusion Tensor Imaging Study

    SciTech Connect

    Nagesh, Vijaya Tsien, Christina I.; Chenevert, Thomas L.; Ross, Brian D.; Lawrence, Theodore S.; Junick, Larry; Cao Yue

    2008-03-15

    Purpose: To quantify the radiation-induced changes in normal-appearing white matter before, during, and after radiotherapy (RT) in cerebral tumor patients. Methods and Materials: Twenty-five patients with low-grade glioma, high-grade glioma, or benign tumor treated with RT were studied using diffusion tensor magnetic resonance imaging. The biologically corrected doses ranged from 50 to 81 Gy. The temporal changes were assessed before, during, and to 45 weeks after the start of RT. The mean diffusivity of water (), fractional anisotropy of diffusion, diffusivity perpendicular ({lambda}{sub perpendicular}) and parallel ({lambda}{sub parallel}) to white matter fibers were calculated in normal-appearing genu and splenium of the corpus callosum. Results: In the genu and splenium, fractional anisotropy decreased and , {lambda}{sub parallel}, {lambda}{sub -perpendicular} increased linearly and significantly with time (p < 0.01). At 45 weeks after the start of RT, {lambda}{sub -perpendicular} had increased {approx}30% in the genu and splenium, and {lambda}{sub parallel} had increased 5% in the genu and 9% in the splenium, suggesting that demyelination is predominant. The increases in {lambda}{sub perpendicular} and {lambda}{sub parallel} were dose dependent, starting at 3 weeks and continuing to 32 weeks from the start of RT. The dose-dependent increase in {lambda}{sub perpendicular} and {lambda}{sub parallel} was not sustained after 32 weeks, indicating the transition from focal to diffuse effects. Conclusion: The acute and subacute changes in normal-appearing white matter fibers indicate radiation-induced demyelination and mild structural degradation of axonal fibers. The structural changes after RT are progressive, with early dose-dependent demyelination and subsequent diffuse dose-independent demyelination and mild axonal degradation. Diffusion tensor magnetic resonance imaging is potentially a biomarker for the assessment of radiation-induced white matter injury.

  9. Radiation-Induced Changes in Normal Appearing White Matter in Patients with Cerebral Tumors: A Diffusion Tensor Imaging Study

    PubMed Central

    Nagesh, V.; Tsien, C.I.; Chenevert, T.L.; Ross, B.D.; Lawrence, T.S.; Junck, L.; Cao, Y.

    2008-01-01

    Purpose: To quantify radiation-induced changes in normal appearing white matter (NAWM) before, during and after radiation therapy (RT) in cerebral tumor patients. Methods and Materials: Twenty-five patients with low-grade glioma, high-grade glioma or benign tumor treated with RT were studied using diffusion tensor MRI. The biologically corrected doses ranged from 50 to 81 Gy. Temporal changes were assessed before, during, and till 45 weeks after start of RT. The mean diffusivity of water , fractional anisotropy (FA) of diffusion, diffusivity perpendicular (λ⊥) and parallel (λ∥) to white matter fibers were calculated in normal-appearing genu and splenium of the corpus callosum. Results: In the genu and splenium, FA decreased and , λ∥, and λ⊥ increased linearly and significantly over time (p< 0.01). At 45 weeks after start of RT, λ⊥ increased ∼30% in the genu and splenium, while λ∥ increased 5% in the genu and 9% in the splenium, suggesting demyelination is predominant. The increases in λ⊥ and λ∥ were dose-dependent starting at 3 weeks and continuing to 32 weeks from the start of RT. The dose-dependent increase in λ⊥ and λ∥ were not sustained after 32 weeks indicating the transition from the focal to diffuse effects. Conclusions: The acute and sub-acute changes in normal appearing white matter fibers indicate radiation-induced demyelination and mild structural degradation of axonal fibers. The structural changes after RT are progressive, with early dose-dependent demyelination and subsequent diffuse dose-independent demyelination and mild axonal degradation. DT-MR imaging is potentially a marker for assessment of radiation-induced white matter injury. PMID:18313524

  10. Relationship between characteristics on magnetic resonance imaging and motor outcomes in children with cerebral palsy and white matter injury.

    PubMed

    Reid, Susan M; Ditchfield, Michael R; Bracken, Jenny; Reddihough, Dinah S

    2015-01-01

    In a population cohort of children with white matter injury (WMI) and cerebral palsy (CP), we aimed to describe the magnetic resonance imaging (MRI) characteristics, identify key structure-function relationships, and classify the severity of WMI in a clinically relevant way. Stratified on MRI laterality/symmetry, variables indicating the extent and location of cerebral abnormalities for 272 children with CP and WMI on chronic-phase MRI were related to gross motor function and motor topography using univariable and multivariable approaches. We found that symmetrical involvement, severe WM loss in the hemispheres and corpus callosum, and cerebellar involvement were the strongest predictors of poor gross motor function, but the final model explained only a small proportion of the variability. Bilateral, extensive WM loss was more likely to result in quadriplegia, whereas volume loss in the posterior-mid WM more frequently resulted in diplegia. The extent and location of MRI abnormalities differed according to laterality/symmetry; asymmetry was associated with less extensive hemispheric involvement than symmetrical WMI, and unilateral lesions were more focal and located more anteriorly. In summary, laterality/symmetry of WMI, possibly reflecting different pathogenic mechanisms, together with extent of WM loss and cerebellar abnormality predicted gross motor function in CP, but to a limited extent. PMID:26263404

  11. SU-E-J-143: Short- and Near-Term Effects of Proton Therapy On Cerebral White Matter

    SciTech Connect

    Uh, J; Merchant, T; Ogg, R; Sabin, N; Hua, C; Indelicato, D

    2014-06-01

    Purpose: To assess early effects of proton therapy on the structural integrity of cerebral white matter in relation to the subsequent near-term development of such effects. Methods: Sixteen children (aged 2–19 years) with craniopharyngioma underwent proton therapy of 54 Cobalt Gray Equivalent (CGE) in a prospective therapeutic trial. Diffusion tensor imaging (DTI) was performed at baseline before proton therapy and every 3 months thereafter. Tract-based spatial statics analysis of DTI data was performed to derive the fractional anisotropy (FA) and radial diffusivity (RD) in 26 volumes of interest (VOIs). The dose distributions were spatially normalized to identify VOIs prone to high doses. The longitudinal percentage changes of the FA and RD in these VOIs at 3 and 12 months from the baseline were calculated, and their relationships were evaluated. Results: The average dose was highest to the cerebral peduncle (CP), corticospinal tract (CST) in the pons, pontine crossing tract (PCT), anterior/posterior limbs of the internal capsule (ALIC/PLIC), and genu of the corpus callosum (GCC). It ranged from 33.3 GCE (GCC) to 49.7 GCE (CP). A mild but statistically significant (P<0.05) decline of FA was observed 3 months after proton therapy in all VOIs except the PLIC and ranged from −1.7% (ALIC) to −2.8% (PCT). A significant increase of RD was found in the CP (3.5%) and ALIC (2.1%). The average longitudinal change from the baseline was reduced at 12 months for most VOIs. However, the standard deviation increased, indicating that the temporal pattern varied individually. The follow-up measurements at 3 and 12 months correlated for the CP, CST, PCT, and GCC (P < 0.04). Conclusion: DTI data suggest early (3 months) effects of proton therapy on microstructures in the white matter. The subsequent follow-up indicated individual variation of the changes, which was partly implied by the early effects.

  12. The Challenge of Understanding Cerebral White Matter Injury in the Premature Infant

    PubMed Central

    Elitt, Christopher M.; Rosenberg, Paul A.

    2014-01-01

    White matter injury in the premature infant leads to motor and more commonly behavioral and cognitive problems that are a tremendous burden to society. While there has been much progress in understanding unique vulnerabilities of developing oligodendrocytes over the past 30 years, there remain no proven therapies for the premature infant beyond supportive care. The lack of translational progress may be partially explained by the challenge of developing relevant animal models when the etiology remains unclear, as is the case in this disorder. There has been an emphasis on hypoxia-ischemia and infection/inflammation as upstream etiologies, but less consideration of other contributory factors. This review highlights the evolution of white matter pathology in the premature infant, discusses the prevailing proposed etiologies, critically analyzes a sampling of common animal models and provides detailed support for our hypothesis that nutritional and hormonal deprivation may be additional factors playing critical and overlooked roles in white matter pathology in the premature infant. PMID:24838063

  13. Analyses of Disruption of Cerebral White Matter Integrity in Schizophrenia with MR Diffusion Tensor Fiber Tracking Method

    NASA Astrophysics Data System (ADS)

    Yamamoto, Utako; Kobayashi, Tetsuo; Kito, Shinsuke; Koga, Yoshihiko

    We have analyzed cerebral white matter using magnetic resonance diffusion tensor imaging (MR-DTI) to measure the diffusion anisotropy of water molecules. The goal of this study is the quantitative evaluation of schizophrenia. Diffusion tensor images are acquired for patients with schizophrenia and healthy comparison subjects, group-matched for age, sex, and handedness. Fiber tracking is performed on the superior longitudinal fasciculus for the comparison between the patient and comparison groups. We have analysed and compared the cross-sectional area on the starting coronal plane and the mean and standard deviation of the fractional anisotropy and the apparent diffusion coefficient along fibers in the right and left hemispheres. In the right hemisphere, the cross-sectional areas in patient group are significantly smaller than those in the comparison group. Furthermore, in the comparison group, the cross-sectional areas in the right hemisphere are significantly larger than those in the left hemisphere, whereas there is no significant difference in the patient group. These results suggest that we may evaluate the disruption in white matter integrity in schizophrenic patients quantitatively by comparing the cross-sectional area of the superior longitudinal fasciculus in the right and left hemispheres.

  14. Cerebral white matter recovery in abstinent alcoholics—a multimodality magnetic resonance study

    PubMed Central

    Durazzo, Timothy C.; Mon, Anderson; Yeh, Ping-Hong; Meyerhoff, Dieter J.

    2010-01-01

    Most previous neuroimaging studies of alcohol-induced brain injury and recovery thereof during abstinence from alcohol used a single imaging modality. They have demonstrated widespread microstructural, macrostructural or metabolite abnormalities that were partially reversible with abstinence, with the cigarette smoking potentially modulating these processes. The goals of this study were to evaluate white matter injury and recovery thereof, simultaneously with diffusion tensor imaging, magnetic resonance imaging and spectroscopy in the same cohort; and to evaluate the relationships between outcome measures of similar regions. We scanned 16 non-smoking and 20 smoking alcohol-dependent individuals at 1 week of abstinence from alcohol and 22 non-smoking light drinkers using a 1.5 T magnetic resonance scanner. Ten non-smoking alcohol-dependent individuals and 11 smoking alcohol-dependent individuals were re-scanned at 1 month of abstinence. All regional diffusion tensor imaging, magnetic resonance imaging and spectroscopic outcome measures were calculated over comparable volumes of frontal, temporal, parietal and occipital white matter. At 1 week of abstinence and relative to non-smoking light drinkers, non-smoking alcohol-dependent individuals had higher mean diffusivity in frontal, temporal and parietal white matter (all P < 0.008), whereas smoking alcohol-dependent individuals had elevated mean diffusivity only in frontal white matter (P = 0.03). Smoking alcohol-dependent individuals demonstrated lower concentrations of N-acetyl-aspartate (a marker of neuronal viability) in frontal white matter (P = 0.03), whereas non-smoking alcohol-dependent individuals had lower N-acetyl-aspartate in parietal white matter (P = 0.05). These abnormalities were not accompanied by detectable white matter atrophy. However, the patterns of white matter recovery were different between non-smoking alcohol-dependent individuals and smoking alcohol-dependent individuals. In non

  15. Preclinical Cerebral Network Connectivity Evidence of Deficits in Mild White Matter Lesions.

    PubMed

    Liang, Ying; Sun, Xuan; Xu, Shijun; Liu, Yaou; Huang, Ruiwang; Jia, Jianjun; Zhang, Zhanjun

    2016-01-01

    White matter lesions (WMLs) are notable for their high prevalence and have been demonstrated to be a potential neuroimaging biomarker of early diagnosis of Alzheimer's disease. This study aimed to identify the brain functional and structural mechanisms underlying cognitive decline observed in mild WMLs. Multi-domain cognitive tests, as well as resting-state, diffusion tensor and structural images were obtained on 42 mild WMLs and 42 age/sex-matched healthy controls. For each participant, we examined the functional connectivity (FC) of three resting-state networks (RSNs) related to the changed cognitive domains: the default mode network (DMN) and the bilateral fronto-parietal network (FPN). We also performed voxel-based morphometry analysis to compare whole-brain gray matter (GM) volume, atlas-based quantification of the white matter tracts interconnecting the RSNs, and the relationship between FC and structural connectivity. We observed FC alterations in the DMN and the right FPN combined with related white matter integrity disruption in mild WMLs. However, no significant GM atrophy difference was found. Furthermore, the right precuneus FC in the DMN exhibited a significantly negative correlation with the memory test scores. Our study suggests that in mild WMLs, dysfunction of RSNs might be a consequence of decreased white matter structural connectivity, which further affects cognitive performance. PMID:26924981

  16. Preclinical Cerebral Network Connectivity Evidence of Deficits in Mild White Matter Lesions

    PubMed Central

    Liang, Ying; Sun, Xuan; Xu, Shijun; Liu, Yaou; Huang, Ruiwang; Jia, Jianjun; Zhang, Zhanjun

    2016-01-01

    White matter lesions (WMLs) are notable for their high prevalence and have been demonstrated to be a potential neuroimaging biomarker of early diagnosis of Alzheimer’s disease. This study aimed to identify the brain functional and structural mechanisms underlying cognitive decline observed in mild WMLs. Multi-domain cognitive tests, as well as resting-state, diffusion tensor and structural images were obtained on 42 mild WMLs and 42 age/sex-matched healthy controls. For each participant, we examined the functional connectivity (FC) of three resting-state networks (RSNs) related to the changed cognitive domains: the default mode network (DMN) and the bilateral fronto-parietal network (FPN). We also performed voxel-based morphometry analysis to compare whole-brain gray matter (GM) volume, atlas-based quantification of the white matter tracts interconnecting the RSNs, and the relationship between FC and structural connectivity. We observed FC alterations in the DMN and the right FPN combined with related white matter integrity disruption in mild WMLs. However, no significant GM atrophy difference was found. Furthermore, the right precuneus FC in the DMN exhibited a significantly negative correlation with the memory test scores. Our study suggests that in mild WMLs, dysfunction of RSNs might be a consequence of decreased white matter structural connectivity, which further affects cognitive performance. PMID:26924981

  17. Age-related slowing of memory retrieval: Contributions of perceptual speed and cerebral white matter integrity

    PubMed Central

    Bucur, Barbara; Madden, David J.; Spaniol, Julia; Provenzale, James M.; Cabeza, Roberto; White, Leonard E.; Huettel, Scott A.

    2007-01-01

    Previous research suggests that, in reaction time (RT) measures of episodic memory retrieval, the unique effects of adult age are relatively small compared to the effects aging shares with more elementary abilities such as perceptual speed. Little is known, however, regarding the mechanisms of perceptual speed. We used diffusion tensor imaging (DTI) to test the hypothesis that white matter integrity, as indexed by fractional anisotropy (FA), serves as one mechanism of perceptual slowing in episodic memory retrieval. Results indicated that declines in FA in the pericallosal frontal region and in the genu of the corpus callosum, but not in other regions, mediated the relationship between perceptual speed and episodic retrieval RT. This relation held, though to a different degree, for both hits and correct rejections. These findings suggest that white matter integrity in prefrontal regions is one mechanism underlying the relation between individual differences in perceptual speed and episodic retrieval. PMID:17383774

  18. Radial Coherence of Diffusion Tractography in the Cerebral White Matter of the Human Fetus: Neuroanatomic Insights

    PubMed Central

    Xu, Gang; Takahashi, Emi; Folkerth, Rebecca D.; Haynes, Robin L.; Volpe, Joseph J.; Grant, P. Ellen; Kinney, Hannah C.

    2014-01-01

    High angular resolution diffusion imaging (HARDI) demonstrates transient radial coherence of telencephalic white matter in the human fetus. Our objective was to define the neuroanatomic basis of this radial coherence through correlative HARDI- and postmortem tissue analyses. Applying immunomarkers to radial glial fibers (RGFs), axons, and blood vessels in 18 cases (19 gestational weeks to 3 postnatal years), we compared their developmental profiles to HARDI tractography in brains of comparable ages (n = 11). At midgestation, radial coherence corresponded with the presence of RGFs. At 30–31 weeks, the transition from HARDI-defined radial coherence to corticocortical coherence began simultaneously with the transformation of RGFs to astrocytes. By term, both radial coherence and RGFs had disappeared. White matter axons were radial, tangential, and oblique over the second half of gestation, whereas penetrating blood vessels were consistently radial. Thus, radial coherence in the fetal white matter likely reflects a composite of RGFs, penetrating blood vessels, and radial axons of which its transient expression most closely matches that of RGFs. This study provides baseline information for interpreting radial coherence in tractography studies of the preterm brain in the assessment of the encephalopathy of prematurity. PMID:23131806

  19. Maternal Antenatal Complications and the Risk of Neonatal Cerebral White Matter Damage and Later Cerebral Palsy in Children Born at an Extremely Low Gestational Age

    PubMed Central

    Allred, Elizabeth N.; Boggess, Kim A.; Kuban, Karl; O'Shea, T. Michael; Paneth, Nigel

    2009-01-01

    In a 2002–2004 prospective cohort study of deliveries of infants at <28 weeks at 14 US centers, the authors sought the antecedents of white matter damage evident in newborn cranial ultrasound scans (ventriculomegaly and an echolucent lesion) and of cerebral palsy diagnoses at age 2 years. Of the 1,455 infants enrolled, those whose mothers received an antenatal steroid tended to have lower risks of ventriculomegaly and an echolucent lesion than their peers (10% vs. 23%, P < 0.001 and 7% vs. 11%, P = 0.06, respectively). Risk of ventriculomegaly was increased for infants delivered because of preterm labor (adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI): 1.1, 4.9), preterm premature rupture of fetal membranes (OR = 3.6, 95% CI: 1.5, 8.7), and cervical insufficiency (OR = 2.8, 95% CI: 1.4, 5.5) when compared with infants delivered because of preeclampsia. Risk of an echolucent lesion was increased for infants delivered because of preterm labor (OR = 2.7, 95% CI: 1.2, 5.7) and intrauterine growth retardation (OR = 3.3, 95% CI: 1.2, 9.4). The doubling of diparesis risk associated with preterm labor and with preterm premature rupture of fetal membranes did not achieve statistical significance, nor did the doubling of quadriparesis risk and the tripling of diparesis risk associated with cervical insufficiency. PMID:19713285

  20. Asymmetry of cerebral gray and white matter and structural volumes in relation to sex hormones and chromosomes

    PubMed Central

    Savic, Ivanka

    2014-01-01

    Whilst many studies show sex differences in cerebral asymmetry, their mechanisms are still unknown. This report describes the potential impact of sex hormones and sex chromosomes by comparing MR data from 39 male and 47 female controls and 33 men with an extra X-chromosome (47,XXY). Methods: Regional asymmetry in gray and white matter volumes (GMV and WMV) was calculated using voxel based moprhometry (SPM5), by contrasting the unflipped and flipped individual GMV and WMV images. In addition, structural volumes were calculated for the thalamus, caudate, putamen, amygdala, and hippocampus, using the FreeSurfer software. Effects of plasma testosterone and estrogen on the GMV and WMV, as well on the right/left ratios of the subcortical volumes were tested by multi-regression analysis. Results: All three groups showed a leftward asymmetry in the motor cortex and the planum temporale, and a rightward asymmetry of the middle occipital cortex. Both asymmetries were more pronounced in 46,XY males than 46,XX females and 47,XXY males, and were positively correlated with testosterone levels. There was also a rightward asymmetry of the vermis and leftward GMV asymmetry in the cerebellar hemispheres in all groups. Notably, cerebellar asymmetries were larger in 46,XX females and 47,XXY males, but were not related to sex hormone levels. No asymmetry differences between 46,XX females and 47,XXY males, and no overall effects of brain size were detected. Conclusion: The asymmetry in the planum temporale area and the occipital cortex seem related to processes associated with testosterone, whereas the observed cerebellar asymmetries suggest a link with X-chromosome escapee genes. Sex differences in cerebral asymmetry are moderated by sex hormones and X-chromosome genes, in a regionally differentiated manner. PMID:25505869

  1. Developmental changes in cerebral white matter microstructure in a disorder of lysosomal storage.

    PubMed

    Bava, Sunita; Theilmann, Rebecca J; Sach, Miriam; May, Susanne J; Frank, Lawrence R; Hesselink, John R; Vu, Duc; Trauner, Doris A

    2010-02-01

    The goal of this work was to study white matter (WM) integrity in children with cystinosis, a rare lysosomal storage disorder resulting in cystine accumulation in peripheral and central nervous system tissue. Based on previous reports of cystine crystal formation in myelin precursors as well as evidence for specific cognitive deficits in visuospatial functioning, diffusion tensor imaging (DTI) was applied to 24 children with cystinosis (age 3-7 years) and to 24 typically developing age-matched controls. Scalar diffusion indices, fractional anisotropy (FA) and mean diffusivity (MD), were examined in manually defined regions of interest within the parietal and inferior temporal lobes. Diffusion indices were correlated with performance on measures of visuospatial cognition and with white blood cell cystine levels. Bilaterally decreased FA and increased MD were evident in the inferior and superior parietal lobules in children with cystinosis, with comparable FA and MD to controls in inferior temporal WM, and implicate a dissociation of the dorsal and ventral visual pathways. In older cystinosis children (age>5), diminutions in visuospatial performance were associated with reduced FA in the right inferior parietal lobule. In addition, increased MD was found in the presence of high cystine levels in all children with cystinosis. This study provides new information that the average diffusion properties in children with cystinosis deviate from typically developing children. Findings suggest the presence of early microstructural WM changes in addition to a secondary effect of cystine accumulation. These alterations may impact the development of efficient fiber networks important for visuospatial cognition. PMID:19427638

  2. Proinflammatory cytokine-receptor interaction model improves the predictability of cerebral white matter injury in preterm infants.

    PubMed

    Bass, W Thomas; Buescher, E Stephen; Hair, Pamela S; White, Larry E; Welch, J Camille; Burke, Bonnie L

    2008-04-01

    Proinflammatory cytokines have been variably linked to development of cerebral white matter injury (WMI) in preterm infants. Because soluble receptors tightly control cytokine bioactivity, we modeled cytokine-receptor interaction as a predictor of WMI. Plasma from 100 preterm infants was assayed for cytokines (tumor necrosis factor alpha, interleukin (IL-1beta, IL-6) and their soluble receptors (sTNF-RI), sTNF-RII, sIL-1RA, and sIL-6R). Cranial ultrasound (US) results were correlated with cytokine and receptor concentrations individually and with cytokine-receptor interaction models (PROC LOGISTIC; SAS Software). Receiver operating characteristic curves were constructed to determine the predictability of WMI. Fifty-two infants with normal US exams were compared with 21 infants with evidence of WMI. There was no association between individual cytokine or receptor concentrations and the development of WMI. However, modeling cytokines with their soluble receptors significantly improved the predictability of WMI. We concluded that consideration of cytokine-receptor interaction may be more important than individual cytokine concentrations alone in determining the role of inflammation in the pathogenesis of WMI in preterm infants. PMID:18548393

  3. Altered white matter integrity and functional connectivity of hyperacute-stage cerebral ischemia in a rat model.

    PubMed

    Cha, Jihoon; Kim, Sung Tae; Jung, Won Beom; Han, Yong Hee; Im, Geun Ho; Lee, Jung Hee

    2016-10-01

    Ischemic stroke is accompanied by structural deformation and functional deficits in the affected hemisphere. Within a couple of hours after symptom onset, the accurate identification of brain characteristics is critical to design the therapeutic strategies and it can potentially improve overall brain tissue viability by minimizing irreversible brain damage. In this study, white matter integrity and functional connectivity within 2-4h after right middle cerebral artery occlusion in rats were investigated using multimodal magnetic resonance imaging. During this stage, diffusion tensor image (DTI) revealed that fractional anisotropy along the ipsilesional external capsule was slightly increased as compared with preoperative baseline. Resting state functional MRI (rs-fMRI) showed that the inter-hemispheric functional connectivities from primary motor (M1), primary somatosensory of forelimb (S1FL), and barrel field (S1BF) seeds were considerably reduced at the hyperacute stage. Fractional amplitudes of low frequency fluctuations (fALFF) from rs-fMRI were significantly enhanced at the hyperacute stage in the frequency spectrum between 0.01 and 0.08Hz. In addition, the changes in fALFF were negatively correlated with the number of functionally connected voxels in M1, S1FL and S1BF. Our results suggest that these techniques are useful tools to evaluate remarkable brain changes in the hyperacute stage of ischemic stroke. PMID:27108358

  4. Alterations in Cerebral White Matter and Neuropsychology in Patients with Cirrhosis and Falls

    PubMed Central

    Gómez-Ansón, Beatriz; Román, Eva; Fernández de Bobadilla, Ramón; Pires-Encuentra, Patricia; Díaz-Manera, Jordi; Núñez, Fidel; Martinez-Horta, Saül; Vives-Gilabert, Yolanda; Pagonabarraga, Javier; Kulisevsky, Jaume; Guarner, Carlos; Soriano, Germán

    2015-01-01

    Background & Aim Falls are frequent in patients with cirrhosis but underlying mechanisms are unknown. The aim was to determine the neuropsychological, neurological and brain alterations using magnetic resonance-diffusion tensor imaging (MR-DTI) in cirrhotic patients with falls. Patients and methods Twelve patients with cirrhosis and falls in the previous year were compared to 9 cirrhotic patients without falls. A comprehensive neuropsychological and neurological evaluation of variables that may predispose to falls included: the Mini-Mental State Examination, Psychometric Hepatic Encephalopathy Score (PHES), Parkinson’s Disease-Cognitive Rating Scale, specific tests to explore various cognitive domains, Unified Parkinson’s Disease Rating Scale to evaluate parkinsonism, scales for ataxia and muscular strength, and electroneurography. High-field MR (3T) including DTI and structural sequences was performed in all patients. Results The main neuropsychological findings were impairment in PHES (p = 0.03), Parkinson’s Disease-Cognitive Rating Scale (p = 0.04) and in executive (p<0.05) and visuospatial-visuoconstructive functions (p<0.05) in patients with falls compared to those without. There were no statistical differences between the two groups in the neurological evaluation or in the visual assessment of MRI. MR-DTI showed alterations in white matter integrity in patients with falls compared to those without falls (p<0.05), with local maxima in the superior longitudinal fasciculus and corticospinal tract. These alterations were independent of PHES as a covariate and correlated with executive dysfunction (p<0.05). Conclusions With the limitation of the small sample size, our results suggest that patients with cirrhosis and falls present alterations in brain white matter tracts related to executive dysfunction. These alterations are independent of PHES impairment. PMID:25793766

  5. [A case of simple form of sudanophilic leukodystrophy of a child which showed a marked loss of cerebral white matter and fatty liver].

    PubMed

    Hayashi, K; Taguchi, K; Tsutsumi, A; Ogawa, K; Fujita, H; Hiramoto, A; Taki, T

    1985-10-01

    A sporadic case of sudanophilic leukodystrophy of the simple form (Peiffer) was reported. The patient was three-year-old girl who had suffered from progressive developmental retardation and neurological disorders such as ataxia, cortical blindness and spastic paralysis of the extremities for eighteen months after she had showed normal development till one and a half years old and died from respiratory insufficiency. On admission, computerized tomogram scan demonstrated diffuse low density lesions of the cerebral white matter extending subsequently to the subcortical white matter. Examination of cerebrospinal fluid revealed only slight increase of protein. Lysosomal enzyme activities such as arylsulfatase and beta-galactosidase in the white blood cells were normal except for distinctly low activity of a-mannosidase without any clinical symptoms suggesting a-mannosidase deficiency. Amino acids in blood were normal. The brain weighed 900 gm. On the coronal sections most part of the cerebral white matter was so strongly degenerated and disappeared that the lateral ventricular structure was not discernible. Histologically, a diffuse and symmetrical demylination, loss of axons including U fibers and moderate gliosis were observed in the residual white matter in the cerebrum and pons. There was no inflammatory cells and metachromatic substances. Large amount of sudanophilic droplets showing polarizing cross and needle like crystals were found in the intra- and/or extracytoplasm of macrophages. Demyelinated lesions with little tissue reaction were also found in the cerebellum, medulla oblongata and in pyramidal tracts through midbrain to cervical spinal cord. There were slight loss of neurons and moderate astrocytosis in the cerebral cortex and basal ganglia. There were no Rosenthal fibers and no sparing of islets of myelin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4074573

  6. Cerebral white matter lesions – associations with Aβ isoforms and amyloid PET

    PubMed Central

    van Westen, Danielle; Lindqvist, Daniel; Blennow, Kaj; Minthon, Lennart; Nägga, Katarina; Stomrud, Erik; Zetterberg, Henrik; Hansson, Oskar

    2016-01-01

    Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of β-amyloid (Aβ) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of Aβ in cerebrospinal fluid (CSF) and cortical Aβ in 831 subjects with cognitive performance ranging from normal to Alzheimer’s disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of Aβ38 and Aβ40 were consistently associated with increased WML in all subgroups, while lower levels of CSF Aβ42 were associated with WML mainly in AD. CSF Aβ38 and Aβ40 were associated with regional WML in all regions, while CSF Aβ42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with Aβ isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of Aβ species, particularly of Aβ38 and Aβ40. However, in AD cases, Aβ42 pathology might be associated with WML, especially in the temporal lobe. PMID:26856756

  7. Obesity Associated Cerebral Gray and White Matter Alterations Are Interrelated in the Female Brain

    PubMed Central

    Möller, Harald E.; Anwander, Alfred; Lepsien, Jöran; Schroeter, Matthias L.; Villringer, Arno; Pleger, Burkhard

    2014-01-01

    Obesity is known to affect the brain's gray matter (GM) and white matter (WM) structure but the interrelationship of such changes remains unclear. Here we used T1-weighted magnetic resonance imaging (MRI) in combination with voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) with tract-based spatial statistics (TBSS) to assess the relationship between obesity-associated alterations of gray matter density (GMD) and anisotropic water diffusion in WM, respectively. In a small cohort of lean to obese women, we confirmed previous reports of obesity-associated alterations of GMD in brain regions involved in executive control (i.e., dorsolateral prefrontal cortex, DLPFC) and habit learning (i.e., dorsal striatum). Gray matter density alterations of the DLPFC were negatively correlated with radial diffusivity in the entire corpus callosum. Within the genu of the corpus callosum we found a positive correlation with axial diffusivity. In posterior region and inferior areas of the body of the corpus callosum, axial diffusivity correlated negatively with altered GMD in the dorsal striatum. These findings suggest that, in women, obesity-related alterations of GMD in brain regions involved in executive control and habit learning might relate to alterations of associated WM fiber bundles within the corpus callosum. PMID:25494174

  8. Characterization of Cerebral White Matter Properties Using Quantitative Magnetic Resonance Imaging Stains

    PubMed Central

    Hurley, Samuel A.; Samsonov, Alexey A.; Adluru, Nagesh; Hosseinbor, Ameer Pasha; Mossahebi, Pouria; Tromp, Do P.M.; Zakszewski, Elizabeth; Field, Aaron S.

    2011-01-01

    Abstract The image contrast in magnetic resonance imaging (MRI) is highly sensitive to several mechanisms that are modulated by the properties of the tissue environment. The degree and type of contrast weighting may be viewed as image filters that accentuate specific tissue properties. Maps of quantitative measures of these mechanisms, akin to microstructural/environmental-specific tissue stains, may be generated to characterize the MRI and physiological properties of biological tissues. In this article, three quantitative MRI (qMRI) methods for characterizing white matter (WM) microstructural properties are reviewed. All of these measures measure complementary aspects of how water interacts with the tissue environment. Diffusion MRI, including diffusion tensor imaging, characterizes the diffusion of water in the tissues and is sensitive to the microstructural density, spacing, and orientational organization of tissue membranes, including myelin. Magnetization transfer imaging characterizes the amount and degree of magnetization exchange between free water and macromolecules like proteins found in the myelin bilayers. Relaxometry measures the MRI relaxation constants T1 and T2, which in WM have a component associated with the water trapped in the myelin bilayers. The conduction of signals between distant brain regions occurs primarily through myelinated WM tracts; thus, these methods are potential indicators of pathology and structural connectivity in the brain. This article provides an overview of the qMRI stain mechanisms, acquisition and analysis strategies, and applications for these qMRI stains. PMID:22432902

  9. Plasma infusions into porcine cerebral white matter induce early edema, oxidative stress, pro-inflammatory cytokine gene expression and DNA fragmentation: implications for white matter injury with increased blood-brain-barrier permeability.

    PubMed

    Wagner, Kenneth R; Dean, Christopher; Beiler, Shauna; Bryan, David W; Packard, Benjamin A; Smulian, A George; Linke, Michael J; de Courten-Myers, Gabrielle M

    2005-04-01

    Plasma infused into porcine cerebral white matter induces both acute interstitial and delayed vasogenic edema. Edematous white matter contains extracellular plasma proteins and rapidly induces oxidative stress as evidenced by increased protein carbonyl formation and heme oxygenase-1 induction. We tested the hypothesis that edematous white matter would also upregulate pro-inflammatory cytokine gene expression and develop DNA damage. We infused autologous plasma into the frontal hemispheric white matter of pentobarbital-anesthetized pigs. We monitored and controlled physiological variables and froze brains in situ at 1, 4 or 24 hrs. We determined edema volumes by computer-assisted morphometry. We measured white matter protein carbonyl formation by immunoblotting, cytokine gene expression by standard RT-PCR methods and DNA fragmentation by agarose gel electrophoresis. White matter edema developed acutely (1 hr) after plasma infusion and increased significantly in volume between 4 and 24 hrs. Protein carbonyl formation also occurred rapidly in edematous white matter with significant elevations (3 to 4-fold) already present at 1 hr. This increase remained through 24 hrs. Pro-inflammatory cytokine gene expression was also rapidly increased at 1 hr post-infusion. Evidence for DNA fragmentation began at 2 to 4 hrs, and a pattern indicative of both ongoing necrosis and apoptosis was robust by 24 hrs. Plasma protein accumulation in white matter induces acute edema development and a cascade of patho-chemical events including oxidative stress, pro-inflammatory cytokine gene expression and DNA damage. These results suggest that in diseases with increased blood-brain barrier (BBB) permeability or following intracerebral hemorrhage or traumatic brain injury, interstitial plasma can rapidly damage white matter. PMID:16181107

  10. White matter pathology and disconnection in the frontal lobe in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

    PubMed Central

    Craggs, L J L; Yamamoto, Y; Ihara, M; Fenwick, R; Burke, M; Oakley, A E; Roeber, S; Duering, M; Kretzschmar, H; Kalaria, R N

    2014-01-01

    Background Magnetic resonance imaging indicates diffuse white matter (WM) changes are associated with cognitive impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We examined whether the distribution of axonal abnormalities is related to microvascular pathology in the underlying WM. Methods We used post-mortem brains from CADASIL subjects and similar age cognitively normal controls to examine WM axonal changes, microvascular pathology, and glial reaction in up to 16 different regions extending rostro-caudally through the cerebrum. Using unbiased stereological methods, we estimated length densities of affected axons immunostained with neurofilament antibody SMI32. Standard immunohistochemistry was used to assess amyloid precursor protein immunoreactivity per WM area. To relate WM changes to microvascular pathology, we also determined the sclerotic index (SI) in WM arterioles. Results The degree of WM pathology consistently scored higher across all brain regions in CADASIL subjects (P < 0.01) with the WM underlying the primary motor cortex exhibiting the most severe change. SMI32 immunoreactive axons in CADASIL were invariably increased compared with controls (P < 0.01), with most prominent axonal abnormalities observed in the frontal WM (P < 0.05). The SIs of arterioles in CADASIL were increased by 25–45% throughout the regions assessed, with the highest change in the mid-frontal region (P = 0.000). Conclusions Our results suggest disruption of either cortico-cortical or subcortical-cortical networks in the WM of the frontal lobe that may explain motor deficits and executive dysfunction in CADASIL. Widespread WM axonal changes arise from differential stenosis and sclerosis of arterioles in the WM of CADASIL subjects, possibly affecting some axons of projection neurones connecting to targets in the subcortical structures. PMID:23844775

  11. Diffuse reduction of white matter connectivity in cerebral palsy with specific vulnerability of long range fiber tracts.

    PubMed

    Englander, Zoë A; Pizoli, Carolyn E; Batrachenko, Anastasiya; Sun, Jessica; Worley, Gordon; Mikati, Mohamad A; Kurtzberg, Joanne; Song, Allen W

    2013-01-01

    Cerebral palsy (CP) is a heterogeneous group of non-progressive motor disorders caused by injury to the developing fetal or infant brain. Although the defining feature of CP is motor impairment, numerous other neurodevelopmental disabilities are associated with CP and contribute greatly to its morbidity. The relationship between brain structure and neurodevelopmental outcomes in CP is complex, and current evidence suggests that motor and developmental outcomes are related to the spatial pattern and extent of brain injury. Given that multiple disabilities are frequently associated with CP, and that there is increasing burden of neurodevelopmental disability with increasing motor severity, global white matter (WM) connectivity was examined in a cohort of 17 children with bilateral CP to test the hypothesis that increased global WM damage will be seen in the group of severely affected (Gross Motor Function Classification Scale (GMFCS) level of IV) as compared to moderately affected (GMFCS of II or III) individuals. Diffusion tensor tractography was performed and the resulting fibers between anatomically defined brain regions were quantified and analyzed in relation to GMFCS levels. Overall, a reduction in total WM connectivity throughout the brain in severe versus moderate CP was observed, including but not limited to regions associated with the sensorimotor system. Our results also show a diffuse and significant reduction in global inter-regional connectivity between severity groups, represented by inter-regional fiber count, throughout the brain. Furthermore, it was also observed that there is a significant difference (p = 0.02) in long-range connectivity in patients with severe CP as compared to those with moderate CP, whereas short-range connectivity was similar between groups. This new finding, which has not been previously reported in the CP literature, demonstrates that CP may involve distributed, network-level structural disruptions. PMID:24179798

  12. Structural connectivity of the anterior cingulate in children with unilateral cerebral palsy due to white matter lesions

    PubMed Central

    Scheck, Simon M.; Pannek, Kerstin; Raffelt, David A.; Fiori, Simona; Boyd, Roslyn N.; Rose, Stephen E.

    2015-01-01

    In this work we investigate the structural connectivity of the anterior cingulate cortex (ACC) and its link with impaired executive function in children with unilateral cerebral palsy (UCP) due to periventricular white matter lesions. Fifty two children with UCP and 17 children with typical development participated in the study, and underwent diffusion and structural MRI. Five brain regions were identified for their high connectivity with the ACC using diffusion MRI fibre tractography: the superior frontal gyrus, medial orbitofrontal cortex, rostral middle frontal gyrus, precuneus and isthmus cingulate. Structural connectivity was assessed in pathways connecting these regions to the ACC using three diffusion MRI derived measures: fractional anisotropy (FA), mean diffusivity (MD) and apparent fibre density (AFD), and compared between participant groups. Furthermore we investigated correlations of these measures with executive function as assessed by the Flanker task. The ACC–precuneus tract had significantly different MD (p < 0.0001) and AFD (p = 0.0072) between groups, with post-hoc analysis showing significantly increased MD in the right hemisphere of children with left hemiparesis compared with controls. The ACC–superior frontal gyrus tract had significantly different FA (p = 0.0049) and MD (p = 0.0031) between groups. AFD in this tract (contralateral to side of hemiparesis; right hemisphere in controls) showed a significant relationship with Flanker task performance (p = 0.0045, β = −0.5856), suggesting that reduced connectivity correlates with executive dysfunction. Reduced structural integrity of ACC tracts appears to be important in UCP, in particular the connection to the superior frontal gyrus. Although damage to this area is heterogeneous it may be important in early identification of children with impaired executive function. PMID:26640762

  13. Chronic lead treatment accelerates photochemically induced platelet aggregation in cerebral microvessels of mice, in vivo

    SciTech Connect

    Al Dhaheri, A.H.; El-Sabban, F.; Fahim, M.A.

    1995-04-01

    Effects of two chronic treatment levels with lead on platelet aggregation in cerebral (pial) microcirculation of the mouse were investigated. Exposure to lead was made by subcutaneous injections for 7 days of lead acetate dissolved in 5% glucose solution, vehicle. Two doses of lead were used, a low dose of 0.1 mg/kg and a high dose of 1.0 mg/kg. Adult male mice were divided into three groups, 10 each; one group was injected with vehicle (control), another was injected with the low dose, and the third was injected with the high dose. Additional mice were used for the determination of hematological parameters and for the lead level in serum of the three groups. On the eighth day, platelet aggregation in pial microvessels of these groups of mice was carried out in vivo. Animals were anesthetized (urethane, 1-2 mg/g, ip), the trachea was intubated, and a craniotomy was performed. Platelet aggregation in pial microvessels was induced photochemically, by activation of circulating sodium fluorescein (0.1 mg/25 g, iv) with an intense mercury light. The time required for the first platelet aggregate to appear in pial arterioles was significantly shorter in the lead-treated mice than in control. This effect was in a dose-dependent manner; 113 {+-} 44 sec for low dose and 71 {+-} 18 sec for high dose vs 155 {+-} 25 sec for control, P < 0.02 and P < 0.001, respectively. Between the two lead-treated groups, the high dose significantly (P < 0.05) shortened the time to first aggregate. These data evidenced an increased susceptibility to cerebrovascular thrombosis as a result of exposure to lead. 26 refs., 4 figs., 2 tabs.

  14. Complications Following Linear Accelerator Based Stereotactic Radiation for Cerebral Arteriovenous Malformations

    SciTech Connect

    Skjoth-Rasmussen, Jane; Roed, Henrik; Ohlhues, Lars; Jespersen, Bo; Juhler, Marianne

    2010-06-01

    Purpose: Primarily, gamma knife centers are predominant in publishing results on arteriovenous malformations (AVM) treatments including reports on risk profile. However, many patients are treated using a linear accelerator-most of these at smaller centers. Because this setting is different from a large gamma knife center, the risk profile at Linac departments could be different from the reported experience. Prescribed radiation doses are dependent on AVM volume. This study details results from a medium sized Linac department center focusing on risk profiles. Method and Materials: A database was searched for all patients with AVMs. We included 50 consecutive patients with a minimum of 24 months follow-up (24-51 months). Results: AVM occlusion was verified in 78% of patients (39/50). AVM occlusion without new deficits (excellent outcome) was obtained in 44%. Good or fair outcome (AVM occlusion with mild or moderate new deficits) was seen in 30%. Severe complications after AVM occlusion occurred in 4% with a median interval of 15 months after treatment (range, 1-26 months). Conclusions: We applied an AVM grading score developed at the Mayo Clinic to predict probable outcome after radiosurgery in a large patient population treated with Gamma knife. A cutoff above and below a score of 1.5 could not discriminate between the likelihood of having an excellent outcome (approximately 45%). The chance of having an excellent or good outcome was slightly higher in patients with an AVM score below 1.5 (64% vs. 57%).

  15. Accelerated decline in white matter integrity in clinically normal individuals at risk for Alzheimer's disease.

    PubMed

    Rieckmann, Anna; Van Dijk, Koene R A; Sperling, Reisa A; Johnson, Keith A; Buckner, Randy L; Hedden, Trey

    2016-06-01

    Prior studies have identified white matter abnormalities in Alzheimer's disease (AD). Yet, cross-sectional studies in normal older individuals show little evidence for an association between markers of AD risk (APOE4 genotype and amyloid deposition), and white matter integrity. Here, 108 normal older adults (age, 66-87) with assessments of apolipoprotein e4 (APOE4) genotype and assessment of amyloid burden by positron emission tomography underwent diffusion tensor imaging scans for measuring white matter integrity at 2 time points, on average 2.6 years apart. Linear mixed-effects models showed that amyloid burden at baseline was associated with steeper decline in fractional anisotropy in the parahippocampal cingulum (p < 0.05). This association was not significant between baseline measures suggesting that longitudinal analyses can provide novel insights that are not detectable in cross-sectional designs. Amyloid-related changes in hippocampus volume did not explain the association between amyloid burden and change in fractional anisotropy. The results suggest that accumulation of cortical amyloid and white matter changes in parahippocampal cingulum are not independent processes in individuals at increased risk for AD. PMID:27143434

  16. Comparison of quantitative autoradiographic and xenon-133 clearance methods: correlation of gray and white matter cerebral blood flow with compartmental blood flow indices

    SciTech Connect

    Tuor, U.I.; Fitch, W.; Graham, D.I.; Mendelow, A.D.

    1986-08-01

    The relationships between CBF in gray and white matter to those of the fast and slow components of xenon-133 clearance curves remain uncertain. CBF was measured in 13 anaesthetized baboons under a variety of conditions, using both the xenon-133 clearance technique and (14C)iodoantipyrine quantitative autoradiography. There was a linear relationship between CBF, as determined by the stochastic (height/area) analysis of the clearance curve, and mean CBF determined from the autoradiograms (r = 0.94, p less than 0.001, slope = 0.86 +/- 0.09). There was also a linear correlation between the fast-flow component (measured with xenon-133) and blood flow in the cerebral gray matter (measured with (14C)iodoantipyrine) (r = 0.92, p less than 0.001, slope = 0.69 +/- 0.15) and between the slow-flow component (with xenon-133) and blood flow in white matter (with (14C)iodoantipyrine) (r = 0.79, p less than 0.01, slope = 0.81 +/- 0.10). In the primate brain, the fast- and slow-flow indices therefore appear to be representative of CBF in gray matter and white matter, respectively, whereas the stochastic analysis provides a stable measure of mean CBF within the tissue monitored.

  17. Obstructive Sleep Apnea as a Risk Factor for Cerebral White Matter Change in a Middle-Aged and Older General Population

    PubMed Central

    Kim, Hyun; Yun, Chang-Ho; Thomas, Robert Joseph; Lee, Seung Hoon; Seo, Hyung Suk; Cho, Eo Rin; Lee, Seung Ku; Yoon, Dae Wui; Suh, Sooyeon; Shin, Chol

    2013-01-01

    Study Objective: Obstructive sleep apnea (OSA) contributes to the development of systemic hypertension, and hypertension strongly predicts the development of white matter change (WMC). Thus, it is plausible that OSA mediates WMC. The goal of the current study is to determine whether a contextual relationship exists between OSA and cerebral WMC. Design: Cross-sectional analyses conducted in a population-based study. Setting: Korean community-based sample from the Korean Genome and Epidemiology Study (KoGES) who attended examinations in 2011 at a medical center. Participants: There were 503 individuals (mean ± SD, age 59.63 ± 7.48 y) who were free of previously diagnosed cardiovascular and neurologic diseases. Measurements and Results: Participants underwent 1-night polysomnography and were classified as no OSA (obstructive apnea-hypopnea index [AHI] < 5, n = 289), mild OSA (AHI 5-15, n = 161), and moderate to severe OSA (AHI ≥ 15, n = 53). WMC was identified with brain magnetic resonance imaging (MRI) and was found in 199 individuals (39.56%). Multivariate logistic regression analyses adjusted for covariates revealed that moderate to severe OSA was significantly associated with the presence of WMC (odds ratio [OR] 2.08, 95%, confidence interval [CI] 1.05-4.13) compared with no OSA. Additional adjustment of hypertension to the model did not alter the significance of the association (OR 2.03, 95% CI 1.02-4.05). Conclusions: Moderate to severe OSA is an independent risk factor for WMC in middle-aged and older individuals. Thus, early recognition and treatment of OSA could reduce the risk of stroke and vascular dementia. Citation: Kim H; Yun CH; Thomas RJ; Lee SH; Seo HS; Cho ER; Lee SK; Yoon DW; Suh S; Shin C. Obstructive sleep apnea as a risk factor for cerebral white matter change in a middle-aged and older general population. SLEEP 2013;36(5):709-715. PMID:23633753

  18. Improved Sensitivity to Cerebral White Matter Abnormalities in Alzheimer’s Disease with Spherical Deconvolution Based Tractography

    PubMed Central

    Reijmer, Yael D.; Leemans, Alexander; Heringa, Sophie M.; Wielaard, Ilse; Jeurissen, Ben; Koek, Huiberdina L.; Biessels, Geert Jan

    2012-01-01

    Diffusion tensor imaging (DTI) based fiber tractography (FT) is the most popular approach for investigating white matter tracts in vivo, despite its inability to reconstruct fiber pathways in regions with “crossing fibers.” Recently, constrained spherical deconvolution (CSD) has been developed to mitigate the adverse effects of “crossing fibers” on DTI based FT. Notwithstanding the methodological benefit, the clinical relevance of CSD based FT for the assessment of white matter abnormalities remains unclear. In this work, we evaluated the applicability of a hybrid framework, in which CSD based FT is combined with conventional DTI metrics to assess white matter abnormalities in 25 patients with early Alzheimer’s disease. Both CSD and DTI based FT were used to reconstruct two white matter tracts: one with regions of “crossing fibers,” i.e., the superior longitudinal fasciculus (SLF) and one which contains only one fiber orientation, i.e. the midsagittal section of the corpus callosum (CC). The DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD), obtained from these tracts were related to memory function. Our results show that in the tract with “crossing fibers” the relation between FA/MD and memory was stronger with CSD than with DTI based FT. By contrast, in the fiber bundle where one fiber population predominates, the relation between FA/MD and memory was comparable between both tractography methods. Importantly, these associations were most pronounced after adjustment for the planar diffusion coefficient, a measure reflecting the degree of fiber organization complexity. These findings indicate that compared to conventionally applied DTI based FT, CSD based FT combined with DTI metrics can increase the sensitivity to detect functionally significant white matter abnormalities in tracts with complex white matter architecture. PMID:22952880

  19. Poor Cerebral Inflammatory Response in eIF2B Knock-In Mice: Implications for the Aetiology of Vanishing White Matter Disease

    PubMed Central

    Geva, Michal; Marom, Liraz; Chetrit, David; Ehrlich, Marcelo; Elroy-Stein, Orna

    2012-01-01

    Background Mutations in any of the five subunits of eukaryotic translation initiation factor 2B (eIF2B) can lead to an inherited chronic-progressive fatal brain disease of unknown aetiology termed leucoencephalopathy with vanishing white matter (VWM). VWM is one of the most prevalent childhood white matter disorders, which markedly deteriorates after inflammation or exposure to other stressors. eIF2B is a major housekeeping complex that governs the rate of global protein synthesis under normal and stress conditions. A previous study demonstrated that Eif2b5R132H/R132H mice suffer delayed white matter development and fail to recover from cuprizone-induced demyelination, although eIF2B enzymatic activity in the mutant brain is reduced by merely 20%. Principal Findings Poor astrogliosis was observed in Eif2b5R132H/R132H mice brain in response to systemic stress induced by peripheral injections of lipopolysaccharide (LPS). Even with normal rates of protein synthesis under normal conditions, primary astrocytes and microglia isolated from mutant brains fail to adequately synthesise and secrete cytokines in response to LPS treatment despite proper induction of cytokine mRNAs. Conclusions The mild reduction in eIF2B activity prevents the appropriate increase in translation rates upon exposure to the inflammatory stressor LPS. The data underscore the importance of fully-functional translation machinery for efficient cerebral inflammatory response upon insults. It highlights the magnitude of proficient translation rates in restoration of brain homeostasis via microglia-astrocyte crosstalk. This study is the first to suggest the involvement of microglia in the pathology of VWM disease. Importantly, it rationalises the deterioration of clinical symptoms upon exposure of VWM patients to physiological stressors and provides possible explanation for their high phenotypic variability. PMID:23056417

  20. FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues.

    PubMed

    Schlein, Christian; Talukdar, Saswata; Heine, Markus; Fischer, Alexander W; Krott, Lucia M; Nilsson, Stefan K; Brenner, Martin B; Heeren, Joerg; Scheja, Ludger

    2016-03-01

    FGF21 decreases plasma triglycerides (TGs) in rodents and humans; however, the underlying mechanism or mechanisms are unclear. In the present study, we examined the role of FGF21 in production and disposal of TG-rich lipoproteins (TRLs) in mice. Treatment with pharmacological doses of FGF21 acutely reduced plasma non-esterified fatty acids (NEFAs), liver TG content, and VLDL-TG secretion. In addition, metabolic turnover studies revealed that FGF21 facilitated the catabolism of TRL in white adipose tissue (WAT) and brown adipose tissue (BAT). FGF21-dependent TRL processing was strongly attenuated in CD36-deficient mice and transgenic mice lacking lipoprotein lipase in adipose tissues. Insulin resistance in diet-induced obese and ob/ob mice shifted FGF21 responses from WAT toward energy-combusting BAT. In conclusion, FGF21 lowers plasma TGs through a dual mechanism: first, by reducing NEFA plasma levels and consequently hepatic VLDL lipidation and, second, by increasing CD36 and LPL-dependent TRL disposal in WAT and BAT. PMID:26853749

  1. Mild cognitive impairment, poor episodic memory, and late-life depression are associated with cerebral cortical thinning and increased white matter hyperintensities

    PubMed Central

    Fujishima, Motonobu; Maikusa, Norihide; Nakamura, Kei; Nakatsuka, Masahiro; Matsuda, Hiroshi; Meguro, Kenichi

    2014-01-01

    In various independent studies to date, cerebral cortical thickness and white matter hyperintensity (WMH) volume have been associated with episodic memory, depression, and mild cognitive impairment (MCI). The aim of this study was to uncover variations in cortical thickness and WMH volume in association with episodic memory, depressive state, and the presence of MCI simultaneously in a single study population. The participants were 186 individuals with MCI (clinical dementia rating [CDR] of 0.5) and 136 healthy elderly controls (HCs; CDR of 0) drawn from two community-based cohort studies in northern Japan. We computed cerebral cortical thickness and WMH volume by using MR scans and statistically analyzed differences in these indices between HCs and MCI participants. We also assessed the associations of these indices with memory performance and depressive state in participants with MCI. Compared with HCs, MCI participants exhibited thinner cortices in the temporal and inferior parietal lobes and greater WMH volumes in the corona radiata and semioval center. In MCI participants, poor episodic memory was associated with thinner cortices in the left entorhinal region and increased WMH volume in the posterior periventricular regions. Compared with non-depressed MCI participants, depressed MCI participants showed reduced cortical thickness in the anterior medial temporal lobe and gyrus adjacent to the amygdala bilaterally, as well as greater WMH volume as a percentage of the total intracranial volume (WMHr). A higher WMHr was associated with cortical thinning in the frontal, temporal, and parietal regions in MCI participants. These results demonstrate that episodic memory and depression are associated with both cortical thickness and WMH volume in MCI participants. Additional longitudinal studies are needed to clarify the dynamic associations and interactions among these indices. PMID:25426066

  2. Associations of Sleep Apnea, NRG1 Polymorphisms, Alcohol Consumption, and Cerebral White Matter Hyperintensities: Analysis with Genome-Wide Association Data

    PubMed Central

    Baik, Inkyung; Seo, Hyung Suk; Yoon, Daewui; Kim, Seong Hwan; Shin, Chol

    2015-01-01

    Study Objective: There are few studies on gene-environment interactions with obstructive sleep apnea (OSA). Our study aimed to explore genetic polymorphisms associated with OSA using genome-wide association (GWA) data and evaluate the effects of relevant polymorphisms on the association between risk factors, including obesity and alcohol consumption, and OSA. We also investigated on these associations in relation to cerebral white matter hyperintensities (WMH) on magnetic resonance images. Design: A cross-sectional design. Setting: A polysomnography study embedded in a population-based cohort from the Korean Genome Epidemiology Study was conducted in 2011–2013. Participants: 1,763 participants aged 48–78 years. Results: 251 individuals were identified to have OSA with an apnea-hypopnea index ≥ 15. A common polymorphism of neuregulin-1 gene (NRG1), rs10097555, was selected as the most suggestive locus associated with OSA (P value < 10−5) based on the results of GWA analysis in a matched case-control subsample (n = 470). Among 1,763 participants, we found that the presence of the NRG1 polymorphism is inversely associated with OSA (P value < 0.01) even after taking into account potential risk factors; the multivariate odds ratio (95% confidence interval) for the mutant alleles was 0.57 (0.39–0.82) compared with the wild-type. We observed that this association is modified by alcohol consumption (P < 0.05), not by obesity. We also observed that WMH are positively associated with OSA independent of the NRG1 polymorphism and alcohol consumption (P < 0.05). Conclusions: These findings suggest that the neuregulin-1 gene (NRG1) may be involved in the etiological mechanisms of obstructive sleep apnea (OSA) and that carriers of a particular NRG1 mutation may be less likely to have OSA if they do not drink alcoholic beverages. Citation: Baik I, Seo HS, Yoon D, Kim SH, Shin C. Associations of sleep apnea, NRG1 polymorphisms, alcohol consumption, and cerebral white

  3. Validity of semi-quantitative scale for brain MRI in unilateral cerebral palsy due to periventricular white matter lesions: Relationship with hand sensorimotor function and structural connectivity

    PubMed Central

    Fiori, Simona; Guzzetta, Andrea; Pannek, Kerstin; Ware, Robert S.; Rossi, Giuseppe; Klingels, Katrijn; Feys, Hilde; Coulthard, Alan; Cioni, Giovanni; Rose, Stephen; Boyd, Roslyn N.

    2015-01-01

    Aim To provide first evidence of construct validity of a semi-quantitative scale for brain structural MRI (sqMRI scale) in children with unilateral cerebral palsy (UCP) secondary to periventricular white matter (PWM) lesions, by examining the relationship with hand sensorimotor function and whole brain structural connectivity. Methods Cross-sectional study of 50 children with UCP due to PWM lesions using 3 T (MRI), diffusion MRI and assessment of hand sensorimotor function. We explored the relationship of lobar, hemispheric and global scores on the sqMRI scale, with fractional anisotropy (FA), as a measure of brain white matter microstructure, and with hand sensorimotor measures (Assisting Hand Assessment, AHA; Jebsen–Taylor Test for Hand Function, JTTHF; Melbourne Assessment of Unilateral Upper Limb Function, MUUL; stereognosis; 2-point discrimination). Results Lobar and hemispheric scores on the sqMRI scale contralateral to the clinical side of hemiplegia correlated with sensorimotor paretic hand function measures and FA of a number of brain structural connections, including connections of brain areas involved in motor control (postcentral, precentral and paracentral gyri in the parietal lobe). More severe lesions correlated with lower sensorimotor performance, with the posterior limb of internal capsule score being the strongest contributor to impaired hand function. Conclusion The sqMRI scale demonstrates first evidence of construct validity against impaired motor and sensory function measures and brain structural connectivity in a cohort of children with UCP due to PWM lesions. More severe lesions correlated with poorer paretic hand sensorimotor function and impaired structural connectivity in the hemisphere contralateral to the clinical side of hemiplegia. The quantitative structural MRI scoring may be a useful clinical tool for studying brain structure–function relationships but requires further validation in other populations of CP. PMID:26106533

  4. Massive accumulation of modified tau and severe depletion of normal tau characterize the cerebral cortex and white matter of Alzheimer's disease. Demonstration using the hydrated autoclaving method.

    PubMed Central

    Shin, R. W.; Iwaki, T.; Kitamoto, T.; Sato, Y.; Tateishi, J.

    1992-01-01

    Using the hydrated autoclaving method, a new immunohistochemical procedure to enhance tau immunoreactivity in formalin-fixed brain tissue, the authors recently reported that tau protein is detected in neuronal cell bodies and proximal dendrites, gray matter neuropil, axons, and glial cells in normal human hippocampus and neocortex. In the this study, the authors performed a comparative study of the distribution of normal and modified forms of tau in Alzheimer's disease (AD) and control brains. In the cerebral cortex and white matter of AD brains, a massive accumulation of modified tau and/or severe depletion of normal tau were documented in all the tau compartments. In mild AD cases, gray matter neuropil, axons, and glial cells were less severely involved than neuronal perikarya. In the controls, neuronal perikarya were often involved by modified tau accumulation, but the other compartments showed normal distribution. These observations suggest that modifications of tau which lead to neurofibrillary lesions in AD may begin in neuronal perikarya and extend to the other tau compartments in advanced stages of the disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1373272

  5. Comparison of cerebral blood flow and structural penumbras in relation to white matter hyperintensities: A multi-modal magnetic resonance imaging study

    PubMed Central

    Lahna, David L; Kaye, Jeffrey A; Dodge, Hiroko H; Erten-Lyons, Deniz; Rooney, William D; Silbert, Lisa C

    2016-01-01

    Normal-appearing white matter (NAWM) surrounding WMHs is associated with decreased structural integrity and perfusion, increased risk of WMH growth, and is referred to as the WMH penumbra. Studies comparing structural and cerebral blood flow (CBF) penumbras within the same individuals are lacking, however, and would facilitate our understanding of mechanisms resulting in WM damage. This study aimed to compare both CBF and structural WMH penumbras in non-demented aging. Eighty-two elderly volunteers underwent 3T-MRI including fluid attenuated inversion recovery (FLAIR), pulsed arterial spin labeling and diffusion tensor imaging (DTI). A NAWM layer mask was generated for periventricular and deep WMHs. Mean CBF, DTI-fractional anisotropy (DTI-FA), DTI-mean diffusivity (DTI-MD) and FLAIR intensity for WMHs and its corresponding NAWM layer masks were computed and compared against its mean within total brain NAWM using mixed effects models. For both periventricular and deep WMHs, DTI-FA, DTI-MD and FLAIR intensity changes extended 2-9 mm surrounding WMHs (p ≤ 0.05), while CBF changes extended 13-14 mm (p ≤ 0.05). The CBF penumbra is more extensive than structural penumbras in relation to WMHs and includes WM tissue both with and without microstructural changes. Findings implicate CBF as a potential target for the prevention of both micro and macro structural WM damage. PMID:27270266

  6. Merosin-deficient congenital muscular dystrophy with cerebral white matter changes: a clue to its diagnosis beyond infancy.

    PubMed

    Kumar, Sandeep; Aroor, Shrikiran; Mundkur, Suneel; Kumar, Maneesh

    2014-01-01

    A 6-year-old boy born by a third-degree consanguineous marriage presented with progressive muscle weakness and delayed motor milestones noticed in early infancy with preserved language and social milestones. Examination revealed generalised hypotonia and hyporeflexia. Baseline haematological and biochemical investigations were normal except for mildly elevated creatine kinase. Provisional diagnosis of congenital myopathy was entertained. We performed brain imaging to look for abnormalities associated with congenital muscular dystrophy even though there were only features of myopathy with normal mentation. An MRI of the brain revealed periventricular and subcortical white matter hyperintensities suggestive of leucoencephalopathy. Muscle biopsy findings were consistent with degenerative muscle changes and immunohistochemical staining for merosin was negative, thus confirming the diagnosis of merosin-deficient congenital muscular dystrophy. Supportive care in the form of physiotherapy was initiated. The family was offered genetic counselling in their second pregnancy and immunohistochemistry at 12 weeks confirmed the fetus to be affected, which was then terminated. PMID:24604798

  7. Cerebral Palsy

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Cerebral Palsy KidsHealth > For Teens > Cerebral Palsy Print A A ... do just what everyone else does. What Is Cerebral Palsy? Cerebral palsy (CP) is a disorder of the ...

  8. Voxel-Wise Perfusion Assessment in Cerebral White Matter with PCASL at 3T; Is It Possible and How Long Does It Take?

    PubMed Central

    Skurdal, Mikjel Johannes; Bjørnerud, Atle; van Osch, Matthias J. P.; Nordhøy, Wibeke; Lagopoulos, Jim; Groote, Inge Rasmus

    2015-01-01

    Purpose To establish whether reliable voxel-wise assessment of perfusion in cerebral white matter (WM) is possible using arterial spin labeling (ASL) at 3T in a cohort of healthy subjects. Materials and Methods Pseudo-continuous ASL (PCASL) with background suppression (BS) optimized for WM measurements was performed at 3T in eight healthy male volunteers aged 25–41. Four different labeling schemes were evaluated by varying the labeling duration (LD) and post-labeling delay (PLD). Eight slices with voxel dimension 3.75x3.75x5 mm3 were acquired from the anterosuperior aspect of the brain, and 400 image/control pairs were collected for each run. Rigid head immobilization was applied using individually fitted thermoplastic masks. For each voxel in the resulting ASL time series, the time needed to reach a 95% significance level for the ASL signal to be higher than zero (paired t-test), was estimated. Results The four protocols detected between 88% and 95% (after Bonferroni correction: 75% and 88%) of WM voxels at 95% significance level. In the most efficient sequence, 80% was reached after 5 min and 95% after 53 min (after Bonferroni correction 40% and 88% respectively). For all protocols, the fraction of significant WM voxels increased in an asymptotic fashion with increasing scan time. A small subgroup of voxels was shown to not benefit at all from prolonged measurement. Conclusion Acquisition of a significant ASL signal from a majority of WM voxels is possible within clinically acceptable scan times, whereas full coverage needs prohibitively long scan times, as a result of the asymptotic trajectory. PMID:26267661

  9. Cerebral Small Vessel Disease and Arterial Stiffness: Tsunami Effect in the Brain?

    PubMed Central

    Saji, Naoki; Toba, Kenji; Sakurai, Takashi

    2016-01-01

    Background Cerebral small vessel diseases, including silent lacunar infarcts, white matter hyperintensities, and microbleeds, pose a risk for cerebrovascular disease, cognitive impairment, and the geriatric syndrome via effects on arterial stiffness. However, the vascular, physiological, and metabolic roles of arterial stiffness in cerebral small vessel diseases remain unclear. Summary Arterial stiffness can be assessed using various indicators such as the ankle-brachial index, pulse wave velocity, cardio-ankle vascular index, and augmentation index. Arterial stiffness is independently associated with all components of cerebral small vessel disease including silent lacunar infarcts, white matter hyperintensities, and microbleeds, although there are some methodological differences between the various surrogate markers. Evidence of arterial stiffness indicates microvessel arteriosclerosis presenting with vascular endothelial dysfunction. Further, vascular narrowing due to atherosclerosis and vascular stiffness due to lipohyalinosis can accelerate the pulse waves. This hemodynamic stress, pulsatile pressure, or blood pressure variability can cause a ‘tsunami effect’ towards the cerebral parenchyma and lead to cerebral small vessel disease. Previous studies have shown that silent lacunar infarcts and white matter hyperintensities are strongly associated with arterial stiffness. However, the association between microbleeds and arterial stiffness remains controversial, as there are two vessel mechanisms related to microbleeds: cerebral amyloid angiopathy and hypertensive small vessel disease. Key Messages Cerebral small vessel disease with associated arterial stiffness is a risk factor for silent cerebral lesions, stroke, and cognitive impairment. Improvement of the living environment, management of risk factors, and innovation and development of novel drugs that improve arterial stiffness may suppress the progression of cerebral small vessel disease, and may reduce

  10. Cerebral Hypoxia

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Cerebral Hypoxia Information Page Synonym(s): Hypoxia, Anoxia Table of Contents ( ... Trials Organizations Publicaciones en Español What is Cerebral Hypoxia? Cerebral hypoxia refers to a condition in which ...

  11. Analysis of junction temperature and modification of luminous flux degradation for white LEDs in a thermal accelerated reliability test.

    PubMed

    Ke, Hong-Liang; Jing, Lei; Hao, Jian; Gao, Qun; Wang, Yao; Wang, Xiao-Xun; Sun, Qiang; Xu, Zhi-Jun

    2016-08-01

    An accelerated aging test is the main method in evaluation of the reliability of light-emitting diodes (LEDs), and the first goal of this study is to investigate how the junction temperature (Tj) of the LED varies during accelerated aging. The Tj measured by the forward voltage method shows an upward trend over the aging time, which gives a variation about 6°C-8°C after 3,000 h of aging under an ambient temperature of 80°C. The second goal is to investigate how the variation of Tj affects the lifetime estimation. It is verified that at a certain aging stage, as Tj increases, the normalized luminous flux linearly decreases with variation rate of microns (μ) (1/°C). Then, we propose a method to modify the luminous flux degradation with the Tj and μ to meet the requirements of a constant degradation rate in the data fitting. The experimental results show that with the proposed method, the accelerated lifetimes of samples are bigger than that of the current method with increment values from 8.8% to 21.4% in this research. PMID:27505370

  12. Sustained linear acceleration

    NASA Technical Reports Server (NTRS)

    Fraser, T. M.

    1973-01-01

    The subjective effects of sustained acceleration are discussed, including positive, negative, forward, backward, and lateral acceleration effects. Physiological effects, such as retinal and visual response, unconsciousness and cerebral function, pulmonary response, and renal output, are studied. Human tolerance and performance under sustained acceleration are ascertained.

  13. Cerebral Palsy

    MedlinePlus

    ... Loss > Birth defects & other health conditions > Cerebral palsy Cerebral palsy E-mail to a friend Please fill in ... movement problems a child has. What is spastic CP? Spastic means tight or stiff muscles, or muscles ...

  14. Cerebral palsy

    MedlinePlus

    Cerebral palsy is a group of disorders that can involve brain and nervous system functions, such as movement, ... and thinking. There are several different types of cerebral palsy, including spastic, dyskinetic, ataxic, hypotonic, and mixed.

  15. Cerebral Palsy

    MedlinePlus

    Cerebral palsy is a group of disorders that affect a person's ability to move and to maintain balance ... do not get worse over time. People with cerebral palsy may have difficulty walking. They may also have ...

  16. Cerebral Palsy

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS NINDS Cerebral Palsy Information Page Clinical Trials Trial of Erythropoietin Neuroprotection ... en Español Additional resources from MedlinePlus What is Cerebral Palsy? The term cerebral palsy refers to a group ...

  17. Cerebral Aneurysms

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Cerebral Aneurysms Information Page Synonym(s): Aneurysm, Brain Aneurysm Condensed from ... Español Additional resources from MedlinePlus What is Cerebral Aneurysms? A cerebral aneurysm is a weak or thin ...

  18. [Cerebral white matter bundle alterations in patients with dementia of Alzheimer type and patients with multi-infarct dementia--magnetic resonance imaging study].

    PubMed

    Yoshii, F; Shinohara, Y; Duara, R

    1990-01-01

    The widths of the anterior white matter bundle (AWM) and the interhemispheric (AWM-TER) and intrahemispheric (AWM-TRA) bundles at the level of the foramen of Monro on horizontal inversion recovery MRI scans were measured in 17 patients with dementia of Alzheimer type (DAT), 16 patients with multi-infarct dementia (MID) and 47 age-matched normal subjects (NOR). The area of the corpus callosum (CC) on midsagittal spin-echo MRI scans was also measured in 12 DAT, 11 MID and 36 NOR. The Mini-mental score in patients with DAT was 20.8 +/- 5.9, which was not significantly different from that of 22.9 +/- 5.4 in patients with MID. The width of AWM was not significantly decreased in either DAT or MID compared with NOR. However, the width of AWM-TER in DAT and MID showed a significant decrease from that in NOR. The width of AWM-TRA was decreased significantly only in DAT. Compared with NOR, the area of the CC in DAT and MID was decreased by 7.0% (p less than 0.05) and 6.5%, respectively. The white matter bundle has an important role in the connectivity of the brain. Although loss of white matter occurs in both DAT and MID, the change appears more diffuse in DAT than MID. PMID:2331816

  19. Monitoring for volcano-hydrothermal activity using continuous gravity and local ground acceleration measurements: New deployments at Inferno Crater, Waimangu and White Island, New Zealand

    NASA Astrophysics Data System (ADS)

    Jolly, Arthur; Fournier, Nico; Cole-Baker, Jeremy; Miller, Craig

    2010-05-01

    Volcanoes with crater lakes are often characterised by shallow hydrothermal systems which display cyclic behaviour (temperature, lake level, chemistry, etc.) and shallow seismic tremor. Present monitoring programmes in New Zealand include routine collection of these observables, but the associated shallow sub-surface processes are still inadequately modelled and poorly understood. Models would be better constrained with the incorporation of additional geophysical parameters. To this end, we have established a new test programme to continuously monitor for micro-gravity variations at New Zealand volcanoes. We utilise a Micro-g-LaCoste gPhone relative gravity meter having 1 Hz sample rate and a measurement precision of 1 microgal to test the viability of gravity monitoring for volcano-hydrothermal systems. We have initially tested the new sensor in a short term deployment (~2 months) at Inferno Crater, Waimangu, New Zealand. Inferno shows dramatic variations in crater lake level (> 7 m range), temperature (>40o C range) and hydrothermally derived tremor, all over a period of ~5 weeks. The amplitude and period of these observables are ideal for testing gravity variations associated with a cycling hydrothermal system because several cycles can be obtained in a relatively short campaign. We have deployed the gravity sensor into a buried vault having a stable concrete base to minimise local environmental influences. This vault is located ~20 meters from Inferno Lake edge (at high stand) and offers sufficient noise reduction to measure the gravitational effects associated with lake level changes. We will show results for the new gravity meter including raw relative gravity measurements and first order corrections (earth-tide, ocean loading, sensor level, temperature, and barometric pressure) to obtain both residual gravity and overprinted local ground accelerations (earthquakes and local tremor). To examine the effects of local ground vibrations on the gravity meter, we

  20. Cerebral palsy.

    PubMed

    Wimalasundera, Neil; Stevenson, Valerie L

    2016-06-01

    Cerebral palsy has always been known as a disorder of movement and posture resulting from a non-progressive injury to the developing brain; however, more recent definitions allow clinicians to appreciate more than just the movement disorder. Accurate classification of cerebral palsy into distribution, motor type and functional level has advanced research. It also facilitates appropriate targeting of interventions to functional level and more accurate prognosis prediction. The prevalence of cerebral palsy remains fairly static at 2-3 per 1000 live births but there have been some changes in trends for specific causal groups. Interventions for cerebral palsy have historically been medical and physically focused, often with limited evidence to support their efficacy. The use of more appropriate outcome measures encompassing quality of life and participation is helping to deliver treatments which are more meaningful for people with cerebral palsy and their carers. PMID:26837375

  1. TM4SF20 Ancestral Deletion and Susceptibility to a Pediatric Disorder of Early Language Delay and Cerebral White Matter Hyperintensities

    PubMed Central

    Wiszniewski, Wojciech; Hunter, Jill V.; Hanchard, Neil A.; Willer, Jason R.; Shaw, Chad; Tian, Qi; Illner, Anna; Wang, Xueqing; Cheung, Sau W.; Patel, Ankita; Campbell, Ian M.; Gelowani, Violet; Hixson, Patricia; Ester, Audrey R.; Azamian, Mahshid S.; Potocki, Lorraine; Zapata, Gladys; Hernandez, Patricia P.; Ramocki, Melissa B.; Santos-Cortez, Regie L.P.; Wang, Gao; York, Michele K.; Justice, Monica J.; Chu, Zili D.; Bader, Patricia I.; Omo-Griffith, Lisa; Madduri, Nirupama S.; Scharer, Gunter; Crawford, Heather P.; Yanatatsaneejit, Pattamawadee; Eifert, Anna; Kerr, Jeffery; Bacino, Carlos A.; Franklin, Adiaha I.A.; Goin-Kochel, Robin P.; Simpson, Gayle; Immken, Ladonna; Haque, Muhammad E.; Stosic, Marija; Williams, Misti D.; Morgan, Thomas M.; Pruthi, Sumit; Omary, Reed; Boyadjiev, Simeon A.; Win, Kay K.; Thida, Aye; Hurles, Matthew; Hibberd, Martin Lloyd; Khor, Chiea Chuen; Van Vinh Chau, Nguyen; Gallagher, Thomas E.; Mutirangura, Apiwat; Stankiewicz, Pawel; Beaudet, Arthur L.; Maletic-Savatic, Mirjana; Rosenfeld, Jill A.; Shaffer, Lisa G.; Davis, Erica E.; Belmont, John W.; Dunstan, Sarah; Simmons, Cameron P.; Bonnen, Penelope E.; Leal, Suzanne M.; Katsanis, Nicholas; Lupski, James R.; Lalani, Seema R.

    2013-01-01

    White matter hyperintensities (WMHs) of the brain are important markers of aging and small-vessel disease. WMHs are rare in healthy children and, when observed, often occur with comorbid neuroinflammatory or vasculitic processes. Here, we describe a complex 4 kb deletion in 2q36.3 that segregates with early childhood communication disorders and WMH in 15 unrelated families predominantly from Southeast Asia. The premature brain aging phenotype with punctate and multifocal WMHs was observed in ∼70% of young carrier parents who underwent brain MRI. The complex deletion removes the penultimate exon 3 of TM4SF20, a gene encoding a transmembrane protein of unknown function. Minigene analysis showed that the resultant net loss of an exon introduces a premature stop codon, which, in turn, leads to the generation of a stable protein that fails to target to the plasma membrane and accumulates in the cytoplasm. Finally, we report this deletion to be enriched in individuals of Vietnamese Kinh descent, with an allele frequency of about 1%, embedded in an ancestral haplotype. Our data point to a constellation of early language delay and WMH phenotypes, driven by a likely toxic mechanism of TM4SF20 truncation, and highlight the importance of understanding and managing population-specific low-frequency pathogenic alleles. PMID:23810381

  2. TM4SF20 ancestral deletion and susceptibility to a pediatric disorder of early language delay and cerebral white matter hyperintensities.

    PubMed

    Wiszniewski, Wojciech; Hunter, Jill V; Hanchard, Neil A; Willer, Jason R; Shaw, Chad; Tian, Qi; Illner, Anna; Wang, Xueqing; Cheung, Sau W; Patel, Ankita; Campbell, Ian M; Gelowani, Violet; Hixson, Patricia; Ester, Audrey R; Azamian, Mahshid S; Potocki, Lorraine; Zapata, Gladys; Hernandez, Patricia P; Ramocki, Melissa B; Santos-Cortez, Regie L P; Wang, Gao; York, Michele K; Justice, Monica J; Chu, Zili D; Bader, Patricia I; Omo-Griffith, Lisa; Madduri, Nirupama S; Scharer, Gunter; Crawford, Heather P; Yanatatsaneejit, Pattamawadee; Eifert, Anna; Kerr, Jeffery; Bacino, Carlos A; Franklin, Adiaha I A; Goin-Kochel, Robin P; Simpson, Gayle; Immken, Ladonna; Haque, Muhammad E; Stosic, Marija; Williams, Misti D; Morgan, Thomas M; Pruthi, Sumit; Omary, Reed; Boyadjiev, Simeon A; Win, Kay K; Thida, Aye; Hurles, Matthew; Hibberd, Martin Lloyd; Khor, Chiea Chuen; Van Vinh Chau, Nguyen; Gallagher, Thomas E; Mutirangura, Apiwat; Stankiewicz, Pawel; Beaudet, Arthur L; Maletic-Savatic, Mirjana; Rosenfeld, Jill A; Shaffer, Lisa G; Davis, Erica E; Belmont, John W; Dunstan, Sarah; Simmons, Cameron P; Bonnen, Penelope E; Leal, Suzanne M; Katsanis, Nicholas; Lupski, James R; Lalani, Seema R

    2013-08-01

    White matter hyperintensities (WMHs) of the brain are important markers of aging and small-vessel disease. WMHs are rare in healthy children and, when observed, often occur with comorbid neuroinflammatory or vasculitic processes. Here, we describe a complex 4 kb deletion in 2q36.3 that segregates with early childhood communication disorders and WMH in 15 unrelated families predominantly from Southeast Asia. The premature brain aging phenotype with punctate and multifocal WMHs was observed in ~70% of young carrier parents who underwent brain MRI. The complex deletion removes the penultimate exon 3 of TM4SF20, a gene encoding a transmembrane protein of unknown function. Minigene analysis showed that the resultant net loss of an exon introduces a premature stop codon, which, in turn, leads to the generation of a stable protein that fails to target to the plasma membrane and accumulates in the cytoplasm. Finally, we report this deletion to be enriched in individuals of Vietnamese Kinh descent, with an allele frequency of about 1%, embedded in an ancestral haplotype. Our data point to a constellation of early language delay and WMH phenotypes, driven by a likely toxic mechanism of TM4SF20 truncation, and highlight the importance of understanding and managing population-specific low-frequency pathogenic alleles. PMID:23810381

  3. Cerebral palsy.

    PubMed

    Graham, H Kerr; Rosenbaum, Peter; Paneth, Nigel; Dan, Bernard; Lin, Jean-Pierre; Damiano, Diane L; Becher, Jules G; Gaebler-Spira, Deborah; Colver, Allan; Reddihough, Dinah S; Crompton, Kylie E; Lieber, Richard L

    2016-01-01

    Cerebral palsy is the most common cause of childhood-onset, lifelong physical disability in most countries, affecting about 1 in 500 neonates with an estimated prevalence of 17 million people worldwide. Cerebral palsy is not a disease entity in the traditional sense but a clinical description of children who share features of a non-progressive brain injury or lesion acquired during the antenatal, perinatal or early postnatal period. The clinical manifestations of cerebral palsy vary greatly in the type of movement disorder, the degree of functional ability and limitation and the affected parts of the body. There is currently no cure, but progress is being made in both the prevention and the amelioration of the brain injury. For example, administration of magnesium sulfate during premature labour and cooling of high-risk infants can reduce the rate and severity of cerebral palsy. Although the disorder affects individuals throughout their lifetime, most cerebral palsy research efforts and management strategies currently focus on the needs of children. Clinical management of children with cerebral palsy is directed towards maximizing function and participation in activities and minimizing the effects of the factors that can make the condition worse, such as epilepsy, feeding challenges, hip dislocation and scoliosis. These management strategies include enhancing neurological function during early development; managing medical co-morbidities, weakness and hypertonia; using rehabilitation technologies to enhance motor function; and preventing secondary musculoskeletal problems. Meeting the needs of people with cerebral palsy in resource-poor settings is particularly challenging. PMID:27188686

  4. Oligodendrogenesis after cerebral ischemia

    PubMed Central

    Zhang, Ruilan; Chopp, Michael; Zhang, Zheng Gang

    2013-01-01

    Neural stem cells in the subventricular zone (SVZ) of the lateral ventricle of adult rodent brain generate oligodendrocyte progenitor cells (OPCs) that disperse throughout the corpus callosum and striatum where some of OPCs differentiate into mature oligodendrocytes. Studies in animal models of stroke demonstrate that cerebral ischemia induces oligodendrogenesis during brain repair processes. This article will review evidence of stroke-induced proliferation and differentiation of OPCs that are either resident in white matter or are derived from SVZ neural progenitor cells and of therapies that amplify endogenous oligodendrogenesis in ischemic brain. PMID:24194700

  5. Traumatic Brain Injury by a Closed Head Injury Device Induces Cerebral Blood Flow Changes and Microhemorrhages

    PubMed Central

    Kallakuri, Srinivasu; Bandaru, Sharath; Zakaria, Nisrine; Shen, Yimin; Kou, Zhifeng; Zhang, Liying; Haacke, Ewart Mark; Cavanaugh, John M

    2015-01-01

    Objectives: Traumatic brain injury is a poly-pathology characterized by changes in the cerebral blood flow, inflammation, diffuse axonal, cellular, and vascular injuries. However, studies related to understanding the temporal changes in the cerebral blood flow following traumatic brain injury extending to sub-acute periods are limited. In addition, knowledge related to microhemorrhages, such as their detection, localization, and temporal progression, is important in the evaluation of traumatic brain injury. Materials and Methods: Cerebral blood flow changes and microhemorrhages in male Sprague Dawley rats at 4 h, 24 h, 3 days, and 7 days were assessed following a closed head injury induced by the Marmarou impact acceleration device (2 m height, 450 g brass weight). Cerebral blood flow was measured by arterial spin labeling. Microhemorrhages were assessed by susceptibility-weighted imaging and Prussian blue histology. Results: Traumatic brain injury rats showed reduced regional and global cerebral blood flow at 4 h and 7 days post-injury. Injured rats showed hemorrhagic lesions in the cortex, corpus callosum, hippocampus, and brainstem in susceptibility-weighted imaging. Injured rats also showed Prussian blue reaction products in both the white and gray matter regions up to 7 days after the injury. These lesions were observed in various areas of the cortex, corpus callosum, hippocampus, thalamus, and midbrain. Conclusions: These results suggest that changes in cerebral blood flow and hemorrhagic lesions can persist for sub-acute periods after the initial traumatic insult in an animal model. In addition, microhemorrhages otherwise not seen by susceptibility-weighted imaging are present in diverse regions of the brain. The combination of altered cerebral blood flow and microhemorrhages can potentially be a source of secondary injury changes following traumatic brain injury and may need to be taken into consideration in the long-term care of these cases. PMID:26605126

  6. Cerebral angiography

    MedlinePlus

    ... Cerebral angiography is done in the hospital or radiology center. You lie on an x-ray table. ... be done in preparation for medical treatment (interventional radiology procedures) by way of certain blood vessels. What ...

  7. Cerebral Palsy

    MedlinePlus

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Cerebral palsy (CP) is a group of disorders that affect a ... ability to move and maintain balance and posture. CP is the most common motor disability in childhood. ...

  8. Cerebral Arteriosclerosis

    MedlinePlus

    ... Cerebral arteriosclerosis is the result of thickening and hardening of the walls of the arteries in the ... cause an ischemic stroke. When the thickening and hardening is uneven, arterial walls can develop bulges (called ...

  9. Cerebral palsy - resources

    MedlinePlus

    Resources - cerebral palsy ... The following organizations are good resources for information on cerebral palsy : National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/disorders/cerebral_palsy/cerebral_palsy. ...

  10. Cerebral Palsy (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Cerebral Palsy KidsHealth > For Parents > Cerebral Palsy Print A A ... kids who are living with the condition. About Cerebral Palsy Cerebral palsy is one of the most common ...

  11. Beyond Black and White.

    ERIC Educational Resources Information Center

    Comer, James P.

    Black and white conflict is a by-product of a more basic problem: the failure of this society to develop a social system that enables all people to meet their basic human needs at a reasonable level. Until this is done, we will not be able to move beyond black and white. The underlying problem is related to a sudden acceleration of human history…

  12. Employees with Cerebral Palsy

    MedlinePlus

    ... Resources Home | Accommodation and Compliance Series: Employees with Cerebral Palsy (CP) By Eddie Whidden, MA Preface Introduction Information About ... SOAR) at http://AskJAN.org/soar. Information about Cerebral Palsy (CP) What is CP? Cerebral palsy is a ...

  13. Cerebral Aneurysms Fact Sheet

    MedlinePlus

    ... Awards Enhancing Diversity Find People About NINDS Cerebral Aneurysms Fact Sheet See a list of all NINDS ... I get more information? What is a cerebral aneurysm? A cerebral aneurysm (also known as an intracranial ...

  14. Cerebral malaria.

    PubMed

    Postels, Douglas G; Birbeck, Gretchen L

    2013-01-01

    Malaria, the most significant parasitic disease of man, kills approximately one million people per year. Half of these deaths occur in those with cerebral malaria (CM). The World Health Organization (WHO) defines CM as an otherwise unexplained coma in a patient with malarial parasitemia. Worldwide, CM occurs primarily in African children and Asian adults, with the vast majority (greater than 90%) of cases occurring in children 5 years old or younger in sub-Saharan Africa. The pathophysiology of the disease is complex and involves infected erythrocyte sequestration, cerebral inflammation, and breakdown of the blood-brain barrier. A recently characterized malarial retinopathy is visual evidence of Plasmodium falciparum's pathophysiological processes occurring in the affected patient. Treatment consists of supportive care and antimalarial administration. Thus far, adjuvant therapies have not been shown to improve mortality rates or neurological outcomes in children with CM. For those who survive CM, residual neurological abnormalities are common. Epilepsy, cognitive impairment, behavioral disorders, and gross neurological deficits which include motor, sensory, and language impairments are frequent sequelae. Primary prevention strategies, including bed nets, vaccine development, and chemoprophylaxis, are in varied states of development and implementation. Continuing efforts to find successful primary prevention options and strategies to decrease neurological sequelae are needed. PMID:23829902

  15. White matter dementia in CADASIL.

    PubMed

    Filley, C M; Thompson, L L; Sze, C I; Simon, J A; Paskavitz, J F; Kleinschmidt-DeMasters, B K

    1999-03-01

    Cerebral white matter disorders may be associated with profound neurobehavioral dysfunction. We report a 62-year-old man who had a slowly progressive 25-year history of personality change, psychosis, mood disorder, and dementia. Neurologic examination disclosed abulia, impaired memory retrieval, and preserved language, with only minimal motor impairment. Neuropsychological testing found a sustained attention deficit, cognitive slowing, impaired learning with intact recognition, and perseveration. Magnetic resonance imaging of the brain revealed extensive leukoencephalopathy. Right frontal brain biopsy showed ill-defined white matter pallor with hyaline narrowing of white matter arterioles. Granular osmiophilic material adjacent to vascular smooth muscle cells on electron microscopy of a skin biopsy, and an arginine for cysteine replacement at position 169 in the 4 EGF motif of the notch 3 region on chromosome 19q12 established the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This case illustrates that CADASIL can manifest as an isolated neurobehavioral disorder over an extended time period. The dementia associated with CADASIL closely resembles that which may occur with other white matter disorders, and represents an example of white matter dementia. PMID:10371078

  16. Cerebral perturbations during exercise in hypoxia.

    PubMed

    Verges, Samuel; Rupp, Thomas; Jubeau, Marc; Wuyam, Bernard; Esteve, François; Levy, Patrick; Perrey, Stéphane; Millet, Guillaume Y

    2012-04-15

    Reduction of aerobic exercise performance observed under hypoxic conditions is mainly attributed to altered muscle metabolism due to impaired O(2) delivery. It has been recently proposed that hypoxia-induced cerebral perturbations may also contribute to exercise performance limitation. A significant reduction in cerebral oxygenation during whole body exercise has been reported in hypoxia compared with normoxia, while changes in cerebral perfusion may depend on the brain region, the level of arterial oxygenation and hyperventilation induced alterations in arterial CO(2). With the use of transcranial magnetic stimulation, inconsistent changes in cortical excitability have been reported in hypoxia, whereas a greater impairment in maximal voluntary activation following a fatiguing exercise has been suggested when arterial O(2) content is reduced. Electromyographic recordings during exercise showed an accelerated rise in central motor drive in hypoxia, probably to compensate for greater muscle contractile fatigue. This accelerated development of muscle fatigue in moderate hypoxia may be responsible for increased inhibitory afferent signals to the central nervous system leading to impaired central drive. In severe hypoxia (arterial O(2) saturation <70-75%), cerebral hypoxia per se may become an important contributor to impaired performance and reduced motor drive during prolonged exercise. This review examines the effects of acute and chronic reduction in arterial O(2) (and CO(2)) on cerebral blood flow and cerebral oxygenation, neuronal function, and central drive to the muscles. Direct and indirect influences of arterial deoxygenation on central command are separated. Methodological concerns as well as future research avenues are also considered. PMID:22319046

  17. Radionuclide cerebral perfusion imaging: Normal pattern

    SciTech Connect

    Goldsmith, S.J.; Stritzke, P.; Losonczy, M.; Vallabhajosula, S.; Holan, V.; DaCosta, M.; Muzinic, M.

    1991-12-31

    Regional cerebral perfusion imaging using a new class of {sup 99m}Tc and {sup 123}I labeled compounds which traverse the blood brain barrier and SPECT imaging technology provides an opportunity to assess this physiologic phenomenon during normal cerebral function and as a manifestation of disease in the central nervous system disease. These applications pose a challenge to the nuclear medicine physician for several reasons: (a) the complex and somewhat unfamiliar functional anatomy, (b) the marked regional differences in regional cerebral perfusion at rest, (c) the lack of understanding of the effect of variations in ambient conditions on regional cerebral perfusion. The difficulties in interpretation are augmented by the display itself. There is frequently no difficulty in differentiating between gray and white matter. However, the frequently used {open_quotes}hot body{close_quotes} color maps, introduce a good deal of contrast, producing displays with apparent interruption in regional cortical perfusion whereas black and white displays provide minimal contrast in the regional cortical activity. The authors sought to define how much variation in regional cerebral perfusion is {open_quotes}allowed{close_quotes} under controlled conditions, to establish a basis to interpret if changes in the environment, psychological interventions, or disease states are accompanied by a measurable change. 2 figs., 1 tab.

  18. [Cerebral palsy].

    PubMed

    Malagón Valdez, Jorge

    2007-01-01

    The term cerebral palsy (CP), is used for a great number of clinical neurological syndromes. The syndromes are characterized by having a common cause, motor defects. It is important, because they can cause a brain damage by presenting motor defects and some associated deficiencies, such as mental deficiency, epilepsy, language and visual defects and pseudobulbar paralysis, with the non-evolving fact. Some authors prefer using terms such as "non-evolving encephalopathies". In the treatment the utility of prevention programs of early stimulation and special rehabilitation methods, and treatment of associated deficiencies such as epilepsy, mental deficiency, language, audition and visual problems, and the attention deficit improve the prognosis in an important way. The prognosis depends on the severity of the disease and the associated manifestations. PMID:18422084

  19. Cerebral malaria in the United Kingdom.

    PubMed Central

    Janota, I; Doshi, B

    1979-01-01

    Four fatal cases of cerebral Plasmodium falciparum malaria in English travellers returning from Africa have been seen in the last 13 years. The haemorrhages, accumulations of microglia, and destruction of cerebral white matter around small veins as a result of blockage of cortical capillaries by parasitised red blood corpuscles resemble the effect of fat embolism. Microglia in the lesions is demonstrated by special neuropathological techniques. Attention is drawn to the need for a prompt recognition of malaria since appropriate treatment can be successful. Images Fig. 1 Fig. 2 PMID:389955

  20. Cerebral Hypoperfusion Precedes Nausea During Centrifugation

    NASA Technical Reports Server (NTRS)

    Serrador, Jorge M.; Schlegel, Todd T.; Black, F. Owen; Wood, Scott J.

    2004-01-01

    Nausea and motion sickness are important operational concerns for aviators and astronauts. Understanding underlying mechanisms associated with motion sickness may lead to new treatments. The goal of this work was to determine if cerebral blood flow changes precede the development of nausea in motion sick susceptible subjects. Cerebral flow velocity in the middle cerebral artery (transcranial Doppler), blood pressure (Finapres) and end-tidal CO2 were measured while subjects were rotated on a centrifuge (250 degrees/sec). Following 5 min of rotation, subjects were translated 0.504 m off-center, creating a +lGx centripetal acceleration in the nasal-occipital plane. Ten subjects completed the protocol without symptoms while 5 developed nausea (4 while 6ff-center and 1 while rotating on-center). Prior to nausea, subjects had significant increases in blood pressure (+13plus or minus 3 mmHg, P less than 0.05) and cerebrovascular resistance (+46 plus or minus 17%, P less than 0.05) and decreases in cerebral flow velocity both in the second (-13 plus or minus 4%) and last minute (-22 plus or minus 5%) before symptoms (P less than 0.05). In comparison, controls demonstrated no change in blood pressure or cerebrovascular resistance in the last minute of off-center rotation and only a 7 plus or minus 2% decrease in cerebral flow velocity. All subjects had significant hypocapnia (-3.8 plus or minus 0.4 mmHg, P less than 0.05), however this hypocapnia could not fully explain the cerebral hypoperfusion associated with the development of nausea. These data indicate that reductions in cerebral blood flow precede the development of nausea. Further work is necessary to determine what role cerebral hypoperfusion plays in motion sickness and whether cerebral hypoperfusion can be used to predict the development of nausea in susceptible individuals.

  1. Cerebral Contusions and Lacerations

    MedlinePlus

    ... Stretch Additional Content Medical News Cerebral Contusions and Lacerations By James E. Wilberger, MD, Derrick A. Dupre, ... a direct, strong blow to the head. Cerebral lacerations are tears in brain tissue, caused by a ...

  2. United Cerebral Palsy

    MedlinePlus

    ... of UCP blog for the latest updates. United Cerebral Palsy UCP educates, advocates and provides support services to ... Partners Merz Logo Sprint Relay Copyright © 2015 United Cerebral Palsy 1825 K Street NW Suite 600 Washington, DC ...

  3. Cerebral amyloid angiopathy

    MedlinePlus

    Cerebral amyloid angiopathy is a neurological condition in which proteins called amyloid build up on the walls of the arteries ... The cause of cerebral amyloid angiopathy is unknown. Sometimes, it ... Persons with this condition have deposits of amyloid protein ...

  4. Aging and Cerebral Palsy.

    ERIC Educational Resources Information Center

    Networker, 1993

    1993-01-01

    This special edition of "The Networker" contains several articles focusing on aging and cerebral palsy (CP). "Aging and Cerebral Palsy: Pathways to Successful Aging" (Jenny C. Overeynder) reports on the National Invitational Colloquium on Aging and Cerebral Palsy held in April 1993. "Observations from an Observer" (Kathleen K. Barrett) describes…

  5. Vanishing White Matter Disease: A Review with Focus on Its Genetics

    ERIC Educational Resources Information Center

    Pronk, Jan C.; van Kollenburg, Barbara; Scheper, Gert C.; van der Knaap, Marjo S.

    2006-01-01

    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…

  6. White House

    MedlinePlus

    ... Check out the most popular infographics and videos Photos View the photo of the day and other galleries Video Gallery ... your questions or your story with President Obama. Photo of the Day Explore the White House Photo ...

  7. What's new in cerebral palsy.

    PubMed

    JONES, M H

    1953-11-01

    Among new researches bearing on cerebral palsy are the growth of brain cells in tissue cultures for experimentation; the use of polysaccharides to prevent the formation of a glial barrier to nerve growth after injury; observation of changes in reactions of neurons at various stages of development; the finding of hypernatremia and hyperchloremia in lesions of the frontal lobe and the thalamus; stimulation of cerebral blood flow by injection of sodium bicarbonate and retardation with ammonium chloride; and studies of serial sections of brains of palsied children who died. Study of development in the early months of life has made possible the detection of significant abnormalities in behavior early in life. Loss of hearing may be tested in very young children by measuring minute variations in electrical resistance of the skin upon auditory stimulation of the sympathetic nervous system. Conditions which have been described as having been confused with cerebral palsy are dislocation of a cervical vertebra, hereditary spastic paraplegia, transverse myelopathy, injury to the spinal cord or cauda equina by anomalous growths of the spine, and also encephalitis and meningitis. Sedation has proved a valuable adjunct to electroencephalographic study of cerebral palsy. Better criteria for abnormality in the young child should be determined and the application of them more clearly standardized. Simple exercises are useful for early training of palsied children to stimulate development. "Crossed laterality"-the dominant eye being contralateral to the preferred hand-has been counteracted by special training with great success in eliminating emotional and behavior problems and accelerating development.Recent studies indicate that only 50 per cent of cerebral palsy patients have normal or better intelligence. Subluxation of the hip joint, a common deformity associated with cerebral palsy, can sometimes be corrected by operation if detected at an early stage. Radical ablation of

  8. Evaluating CT Perfusion Deficits in Global Cerebral Edema after Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    Baradaran, H.; Fodera, V.; Mir, D.; Kesavobhotla, K.; Ivanidze, J.; Ozbek, U.; Gupta, A.; Claassen, J.; Sanelli, P.C.

    2015-01-01

    BACKGROUND AND PURPOSE Global cerebral edema is an independent predictor of mortality and poor outcomes after aneurysmal SAH. Global cerebral edema, a complex disease process, is thought to be associated with an altered cerebral autoregulatory response. We studied the association between cerebral hemodynamics and early global cerebral edema by using CTP. MATERIALS AND METHODS We retrospectively studied consecutive patients with aneurysmal SAH with admission CTP performed at days 0–3. Two neuroradiologists classified global cerebral edema and hydrocephalus on NCCT performed concurrently with CTP. Global cerebral edema was defined as diffuse effacement of the sulci and/or basal cisterns or diffuse disruption of the cerebral gray-white matter junction. CTP was postprocessed into CBF and MTT maps by using a standardized method. Quantitative analysis of CTP was performed by using standard protocol with ROI sampling of the cerebral cortex. The Fisher exact test, Mann-Whitney test, and independent-samples t test were used to determine statistical associations. RESULTS Of the 45 patients included, 42% (19/45) had global cerebral edema and 58% (26/45) did not. Patient groups with and without global cerebral edema were well-matched for demographic and clinical data. Patients with global cerebral edema were more likely to have qualitative global CTP deficits than those without global cerebral edema (P = .001) with an OR = 13.3 (95% CI, 2.09–138.63). Patients with global cerebral edema also had a very strong trend toward statistical significance, with reduced quantitative CBF compared with patients without global cerebral edema (P = .064). CONCLUSIONS Global perfusion deficits are significantly associated with global cerebral edema in the early phase after aneurysmal SAH, supporting the theory that hemodynamic disturbances occur in global cerebral edema. PMID:25977478

  9. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  10. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  11. Cerebral hemiatrophy: a clinicopathological report of two cases with a contribution to pathogenesis and differential diagnosis.

    PubMed

    Vosskämper, M; Schachenmayr, W

    1990-01-01

    "Cerebral hemiatrophy" describes a condition of different etiologies that is characterized by a marked asymmetry of cerebral hemispheres. Case reports of two different forms of cerebral hemiatrophy are presented. In the first case perinatal asphyxia led to severe white matter lesions with predominance on the left side and marked asymmetry of the pyramidal tracts. Symptoms were present immediately after birth ("primary cerebral hemiatrophy"). The second case displayed postictal cerebral hemiatrophy with a widespread loss of cortical neurons of the entire left hemisphere. The disease process started at the age of two years after a widely normal early development ("secondary cerebral hemiatrophy"). A modified classification of cerebral hemiatrophy is presented, and concepts of pathogenesis and differential diagnosis are discussed. PMID:2125535

  12. [Etiology of cerebral palsy].

    PubMed

    Jaisle, F

    1996-01-01

    The "perinatal asphyxia" is regarded to be one of the causes of cerebral palsy, though in the very most of the children with cerebral palsy there is found no hypoxia during labour. It should be mentioned, that the definition of "perinatal" and "asphyxia" neither are unic nor concret. And also there is no correlation between nonreassuring fetal heart rate patterns and acidosis in fetal blood with the incidence of cerebral palsy. Numerous studies in pregnant animals failed in proving an acute intrapartal hypoxia to be the origin of the cerebral palsy. Myers (1975) describes four patterns of anatomic brain damage after different injuries. Only his so called oligo-acidotic hypoxia, which is protracted and lasts over a longer time is leading to brain injury, which can be regarded in analogy to the injury of children with cerebral palsy. Summarising the update publications about the causes of cerebral palsy and the studies in pregnant animals there is no evidence that hypoxia during labour may be the cause of cerebral palsy. There is a great probability of a pre(and post-)natal origin of brain injury (for instance a periventricular leucomalacia found after birth) which leads to cerebral palsy. Short after labour signs of a so called "asphyxia" may occur in addition to this preexisting injury and misrepresent the cause of cerebral palsy. Finally the prepartal injury may cause both: Cerebral palsy and hypoxia. PMID:9035826

  13. [Linear accelerator radiosurgery].

    PubMed

    Brandt, R A; Salvajoli, J V; Oliveira, V C; Carmignani, M; da Cruz, J C; Leal, H D; Ferraz, L

    1995-03-01

    Radiosurgery is the precise radiation of a known intracranial target with a high dose of energy, sparing the adjacent nervous tissue. Technological advances in the construction of linear accelerators, stereotactic instruments and in computer sciences made this technique easier to perform and affordable. The main indications for radiosurgery are inoperable cerebral vascular malformations, vestibular and other cranial schwannomas, skull base meningiomas, deep seated gliomas and cerebral metastases. More recently, the development of fraccionated stereotactic radiotherapy increased the spectrum of indications to bigger lesions and to those adjacent to critical nervous structures. We present our initial experience in the treatment of 31 patients. An adequate control of the neoplastic lesions was obtained and the adequate time of observation is still needed to evaluate the results in arteriovenous malformations. PMID:7575207

  14. White Rock

    NASA Technical Reports Server (NTRS)

    2002-01-01

    (Released 19 April 2002) The Science 'White Rock' is the unofficial name for this unusual landform which was first observed during the Mariner 9 mission in the early 1970's. As later analysis of additional data sets would show, White Rock is neither white nor dense rock. Its apparent brightness arises from the fact that the material surrounding it is so dark. Images from the Mars Global Surveyor MOC camera revealed dark sand dunes surrounding White Rock and on the floor of the troughs within it. Some of these dunes are just apparent in the THEMIS image. Although there was speculation that the material composing White Rock could be salts from an ancient dry lakebed, spectral data from the MGS TES instrument did not support this claim. Instead, the White Rock deposit may be the erosional remnant of a previously more continuous occurrence of air fall sediments, either volcanic ash or windblown dust. The THEMIS image offers new evidence for the idea that the original deposit covered a larger area. Approximately 10 kilometers to the southeast of the main deposit are some tiny knobs of similarly bright material preserved on the floor of a small crater. Given that the eolian erosion of the main White Rock deposit has produced isolated knobs at its edges, it is reasonable to suspect that the more distant outliers are the remnants of a once continuous deposit that stretched at least to this location. The fact that so little remains of the larger deposit suggests that the material is very easily eroded and simply blows away. The Story Fingers of hard, white rock seem to jut out like icy daggers across a moody Martian surface, but appearances can be deceiving. These bright, jagged features are neither white, nor icy, nor even hard and rocky! So what are they, and why are they so different from the surrounding terrain? Scientists know that you can't always trust what your eyes see alone. You have to use other kinds of science instruments to measure things that our eyes can

  15. Cerebral blood flow measured by NMR indicator dilution in cats

    SciTech Connect

    Ewing, J.R.; Branch, C.A.; Helpern, J.A.; Smith, M.B.; Butt, S.M.; Welch, K.M.

    1989-02-01

    We developed techniques to assess the utility of a nuclear magnetic resonance (NMR) indicator for cerebral blood flow studies in cats, using Freon-22 for the first candidate. A PIN-diode-switched NMR experiment allowed the acquisition of an arterial as well as a cerebral fluorine-19 signal proportional to concentration vs. time in a 1.89 T magnet. Mean +/- SD blood:brain partition coefficients for Freon-22 were estimated at 0.93 +/- 0.08 for gray matter and 0.77 +/- 0.12 for white matter. Using maximum-likelihood curve fitting, estimates of mean +/- SD resting cerebral blood flow were 50 +/- 19 ml/100 g-min for gray matter and 5.0 +/- 2.0 ml/100 g-min for white matter. Hypercapnia produced the expected increases in gray and white matter blood flow. The physiologic effects of Freon-22, including an increase in cerebral blood flow itself with administration of 40% by volume, may limit its use as an indicator. Nevertheless, the NMR techniques described demonstrate the feasibility of fluorine-19-labeled compounds as cerebral blood flow indicators and the promise for their use in humans.

  16. Hemiparesis post cerebral malaria

    PubMed Central

    Taiaa, Oumkaltoum; Amil, Touriya; Darbi, Abdelatif

    2015-01-01

    Cerebral malaria is one of the most serious complications in the Plasmodium falciparum infection. In endemic areas, the cerebral malaria interested mainly children. The occurrence in adults is very rare and most interested adult traveling in tropical zones. This case report describes a motor deficit post cerebral malaria in a young adult traveling in malaria endemic area. This complication has been reported especially in children and seems very rare in adults. PMID:25995798

  17. Incidental Cerebral Microbleeds and Cerebral Blood Flow in Elderly Individuals

    PubMed Central

    Gregg, Nicholas M.; Kim, Albert E.; Gurol, M. Edip; Lopez, Oscar L.; Aizenstein, Howard J.; Price, Julie C.; Mathis, Chester A.; James, Jeffrey A.; Snitz, Beth E.; Cohen, Ann D.; Kamboh, M. Ilyas; Minhas, Davneet; Weissfeld, Lisa A.; Tamburo, Erica L.; Klunk, William E.

    2016-01-01

    IMPORTANCE Cerebral microbleeds (CMBs) are collections of blood breakdown products that are a common incidental finding in magnetic resonance imaging of elderly individuals. Cerebral microbleeds are associated with cognitive deficits, but the mechanism is unclear. Studies show that individuals with CMBs related to symptomatic cerebral amyloid angiopathy have abnormal vascular reactivity and cerebral blood flow (CBF), but, to our knowledge, abnormalities in cerebral blood flow have not been reported for healthy individuals with incidental CMBs. OBJECTIVE To evaluate the association of incidental CMBs with resting-state CBF, cerebral metabolism, cerebrovascular disease, β-amyloid (Aβ), and cognition. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study of 55 cognitively normal individuals with a mean (SD) age of 86.8 (2.7) years was conducted from May 1, 2010, to May 1, 2013, in an academic medical center in Pittsburgh; data analysis was performed between June 10, 2013, and April 9, 2015. INTERVENTIONS 3-Tesla magnetic resonance imaging was performed with susceptibility-weighted imaging or gradient-recalled echo to assess CMBs, arterial spin labeling for CBF, and T1- and T2-weighted imaging for atrophy, white matter hyperintensities, and infarcts. Positron emission tomography was conducted with fluorodeoxyglucose to measure cerebral metabolism and Pittsburgh compound B for fibrillar Aβ. Neuropsychological evaluation, including the Clinical Dementia Rating scale, was performed. MAIN OUTCOMES AND MEASURES Magnetic resonance images were rated for the presence and location of CMBs. Lobar CMBs were subclassified as cortical or subcortical. Measurements of CBF, metabolism, and Aβ were compared with the presence and number of CMBs with voxelwise and region-of-interest analyses. RESULTS The presence of cortical CMBs was associated with significantly reduced CBF in multiple regions on voxelwise and region-of-interest analyses (percentage difference in global CBF,

  18. The transcriptome of cerebral ischemia

    PubMed Central

    VanGilder, Reyna L.; Huber, Jason D.; Rosen, Charles L.; Barr, Taura L.

    2015-01-01

    The molecular causality and response to stroke is complex. Yet, much of the literature examining the molecular response to stroke has focused on targeted pathways that have been well-characterized. Consequently, our understanding of stroke pathophysiology has made little progress by way of clinical therapeutics since tissue plasminogen activator was approved for treatment nearly a decade ago. The lack of clinical translation is in part due to neuron-focused studies, preclinical models of cerebral ischemia and the paradoxical nature of neuro-inflammation. With the evolution of the Stroke Therapy Academic Industry Roundtable criteria streamlining research efforts and broad availability of genomic technologies, the ability to decipher the molecular fingerprint of ischemic stroke is on the horizon. This review highlights preclinical microarray findings of the ischemic brain, discusses the transcriptome of cerebral preconditioning and emphasizes the importance of further characterizing the role of the neurovascular unit and peripheral white blood cells in mediating stroke damage and repair within the penumbra. PMID:22381515

  19. [Negative symptoms and cerebral imaging].

    PubMed

    Kaladjian, A; Belzeaux, R; Adida, M; Azorin, J-M

    2015-12-01

    A number of neuroanatomical and neurofonctional abnormalities have been evidenced by cerebral imaging studies in patients suffering from schizophrenia. Nevertheless, those specifically associated with the negative symptoms of this disease are still insufficiently known. This work is a review of selected studies that have assessed the brain correlates of negative symptoms in schizophrenia. Approaches using structural imaging have highlighted reduction of gray matter density or cortical thickness associated with negative symptoms, which is rather sparsely distributed within the frontal and temporal regions, localized nevertheless more particularly in the frontal medial and orbitofrontal areas, as well as the amygdalo-hippocampic complex. These deficits are concurrent with a loss of integrity of the principal paths of white matter tracts between frontal and limbic regions. On the other hand, neurofonctional abnormalities associated with negative symptoms involve especially the frontal areas and limbic striatum. A disturbed functioning within the fronto-striatal loops, related to a striatal dopaminergic deficit, may represent a potential explanatory hypothesis of the negative symptoms of schizophrenia, as suggested by studies using Positron Emission Tomography on this topic or neuroimaging studies on the effects of antipsychotics. A better identification of the cerebral abnormalities associated with the negative dimension of schizophrenia, with regard to the lateralization of these abnormalities or to their changes during the course of the disease, could offer new therapeutic modalities for the treatment of this dimension which, until now, remains few responsive to conventional pharmacological treatments. PMID:26776387

  20. Genetic variation in homocysteine metabolism, cognition, and white matter lesions.

    PubMed

    de Lau, Lonneke M L; van Meurs, Joyce B J; Uitterlinden, André G; Smith, A David; Refsum, Helga; Johnston, Carole; Breteler, Monique M B

    2010-11-01

    Several studies have shown an association between homocysteine concentration and cognitive performance or cerebral white matter lesions. However, variations in genes encoding for enzymes and other proteins that play a role in homocysteine metabolism have hardly been evaluated in relation to these outcome measures. In the population-based Rotterdam Scan Study, we examined the association of seven polymorphisms of genes involved in homocysteine metabolism (MTHFR 677C>T, MTHFR 1298A>C, RFC 80G>A, TC 776C>G, MTR 2756A>G, MTRR 66A>G, and CBS 844ins68) with plasma total homocysteine, cognitive performance, and cerebral white matter lesions among 1011 non-demented elderly participants. Of all the studied polymorphisms, only MTHFR 677C>T was associated with homocysteine concentration. No significant relationship was observed for any of the polymorphisms with cognitive performance or severity of cerebral white matter lesions. PMID:19019492

  1. White phosphorus

    Integrated Risk Information System (IRIS)

    White phosphorus ; CASRN 7723 - 14 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic

  2. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  3. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  4. Cerebral Asymmetries and Reading Acquisition

    ERIC Educational Resources Information Center

    Pirozzolo, Francis J.

    1978-01-01

    Reviewed are historical developments regarding the concepts of cerebral localization, and analyzed are implications of current research on the role of the cerebral hemispheres in reading disorders. (CL)

  5. Long-term cognitive sequelae of cerebral malaria in Vietnam veterans.

    PubMed

    Richardson, E D; Varney, N R; Roberts, R J; Springer, J A; Wood, P S

    1997-01-01

    The brains of fatal cases of cerebral malaria exhibit capillary occlusion, punctiform hemorrhages, and focal necrosis in subcortical white matter. Some studies have suggested that the brain pathology of survivors is similar to that of fatal cases. The purpose of this study was to investigate the hypothesis that cerebral malaria survivors would exhibit neuropsychological impairment due to the residual cerebral damage sustained from the infection. Vietnam veterans reporting a history of cerebral malaria were compared with a group of veterans with a history of combat-related injuries on standard neuropsychological tasks and on dichotic listening (DL). The cerebral malaria group performed worse on memory tasks and exhibited greater clinical impairments on DL, consistent with presumed disruption of subcortical white matter tracts. PMID:16318473

  6. Variants in CUL4B are Associated with Cerebral Malformations

    PubMed Central

    Vulto-van Silfhout, Anneke T.; Nakagawa, Tadashi; Bahi-Buisson, Nadia; Haas, Stefan A.; Hu, Hao; Bienek, Melanie; Vissers, Lisenka E.L.M.; Gilissen, Christian; Tzschach, Andreas; Busche, Andreas; Müsebeck, Jörg; Rump, Patrick; Mathijssen, Inge B.; Avela, Kristiina; Somer, Mirja; Doagu, Fatma; Philips, Anju K.; Rauch, Anita; Baumer, Alessandra; Voesenek, Krysta; Poirier, Karine; Vigneron, Jacqueline; Amram, Daniel; Odent, Sylvie; Nawara, Magdalena; Obersztyn, Ewa; Lenart, Jacek; Charzewska, Agnieszka; Lebrun, Nicolas; Fischer, Ute; Nillesen, Willy M.; Yntema, Helger G.; Järvelä, Irma; Ropers, Hans-Hilger; de Vries, Bert B.A.; Brunner, Han G.; van Bokhoven, Hans; Raymond, F. Lucy; Willemsen, Michèl A.A.P.; Chelly, Jamel; Xiong, Yue; Barkovich, A. James; Kalscheuer, Vera M.; Kleefstra, Tjitske; de Brouwer, Arjan P.M.

    2015-01-01

    Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B. PMID:25385192

  7. Prognostic Impact of Cerebral Small Vessel Disease on Stroke Outcome

    PubMed Central

    Kim, Beom Joon

    2015-01-01

    Cerebral small vessel disease (SVD), which includes white matter hyperintensities (WMHs), silent brain infarction (SBI), and cerebral microbleeds (CMBs), develops in a conjunction of cumulated injuries to cerebral microvascular beds, increased permeability of blood-brain barriers, and chronic oligemia. SVD is easily detected by routine neuroimaging modalities such as brain computed tomography or magnetic resonance imaging. Research has revealed that the presence of SVD markers may increase the risk of future vascular events as well as deteriorate functional recovery and neurocognitive trajectories after stroke, and such an association could also be applied to hemorrhagic stroke survivors. Currently, the specific mechanistic processes leading to the development and manifestation of SVD risk factors are unknown, and further studies with novel methodological tools are warranted. In this review, recent studies regarding the prognostic impact of WMHs, SBI, and CMBs on stroke survivors and briefly summarize the pathophysiological concepts underlying the manifestation of cerebral SVD. PMID:26060797

  8. Cerebral Palsy (CP) Quiz

    MedlinePlus

    ... Submit Button Past Emails CDC Features Pop Quiz: Cerebral Palsy Language: English Español (Spanish) Recommend on Facebook Tweet ... Sandy is the parent of a child with cerebral palsy and the Board President of Gio’s Garden , a ...

  9. Cerebral Small Vessel Disease: Targeting Oxidative Stress as a Novel Therapeutic Strategy?

    PubMed Central

    De Silva, T. Michael; Miller, Alyson A.

    2016-01-01

    Cerebral small vessel disease (SVD) is a major contributor to stroke, and a leading cause of cognitive impairment and dementia. Despite the devastating effects of cerebral SVD, the pathogenesis of cerebral SVD is still not completely understood. Moreover, there are no specific pharmacological strategies for its prevention or treatment. Cerebral SVD is characterized by marked functional and structural abnormalities of the cerebral microcirculation. The clinical manifestations of these pathological changes include lacunar infarcts, white matter hyperintensities, and cerebral microbleeds. The main purpose of this review is to discuss evidence implicating oxidative stress in the arteriopathy of both non-amyloid and amyloid (cerebral amyloid angiopathy) forms of cerebral SVD and its most important risk factors (hypertension and aging), as well as its contribution to cerebral SVD-related brain injury and cognitive impairment. We also highlight current evidence of the involvement of the NADPH oxidases in the development of oxidative stress, enzymes that are a major source of reactive oxygen species in the cerebral vasculature. Lastly, we discuss potential pharmacological strategies for oxidative stress in cerebral SVD, including some of the historical and emerging NADPH oxidase inhibitors. PMID:27014073

  10. White Rock

    NASA Technical Reports Server (NTRS)

    2005-01-01

    14 November 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a portion of the famous 'White Rock' feature in Pollack Crater in the Sinus Sabaeus region of Mars. The light-toned rock is not really white, but its light tone caught the eye of Mars geologists as far back as 1972, when it was first spotted in images acquired by Mariner 9. The light-toned materials are probably the remains of a suite of layered sediments that once spread completely across the interior of Pollack Crater. Dark materials in this image include sand dunes and large ripples.

    Location near: 8.1oS, 335.1oW Image width: width: 3 km (1.9 mi) Illumination from: lower left Season: Southern Summer

  11. White Blood Cell Count

    MedlinePlus

    ... Home Visit Global Sites Search Help? White Blood Cell Count Share this page: Was this page helpful? Also ... Leukocyte Count; White Count Formal name: White Blood Cell Count Related tests: Complete Blood Count , Blood Smear , White ...

  12. Neonatal White Matter Abnormalities an Important Predictor of Neurocognitive Outcome for Very Preterm Children

    PubMed Central

    Woodward, Lianne J.; Clark, Caron A. C.; Bora, Samudragupta; Inder, Terrie E.

    2012-01-01

    Background Cerebral white matter abnormalities on term MRI are a strong predictor of motor disability in children born very preterm. However, their contribution to cognitive impairment is less certain. Objective Examine relationships between the presence and severity of cerebral white matter abnormalities on neonatal MRI and a range of neurocognitive outcomes assessed at ages 4 and 6 years. Design/Methods The study sample consisted of a regionally representative cohort of 104 very preterm (≤32 weeks gestation) infants born from 1998–2000 and a comparison group of 107 full-term infants. At term equivalent, all preterm infants underwent a structural MRI scan that was analyzed qualitatively for the presence and severity of cerebral white matter abnormalities, including cysts, signal abnormalities, loss of white matter volume, ventriculomegaly, and corpus callosal thinning/myelination. At corrected ages 4 and 6 years, all children underwent a comprehensive neurodevelopmental assessment that included measures of general intellectual ability, language development, and executive functioning. Results At 4 and 6 years, very preterm children without cerebral white matter abnormalities showed no apparent neurocognitive impairments relative to their full-term peers on any of the domain specific measures of intelligence, language, and executive functioning. In contrast, children born very preterm with mild and moderate-to-severe white matter abnormalities were characterized by performance impairments across all measures and time points, with more severe cerebral abnormalities being associated with increased risks of cognitive impairment. These associations persisted after adjustment for gender, neonatal medical risk factors, and family social risk. Conclusions Findings highlight the importance of cerebral white matter connectivity for later intact cognitive functioning amongst children born very preterm. Preterm born children without cerebral white matter abnormalities on

  13. Plasma accelerators

    SciTech Connect

    Ruth, R.D.; Chen, P.

    1986-03-01

    In this paper we discuss plasma accelerators which might provide high gradient accelerating fields suitable for TeV linear colliders. In particular we discuss two types of plasma accelerators which have been proposed, the Plasma Beat Wave Accelerator and the Plasma Wake Field Accelerator. We show that the electric fields in the plasma for both schemes are very similar, and thus the dynamics of the driven beams are very similar. The differences appear in the parameters associated with the driving beams. In particular to obtain a given accelerating gradient, the Plasma Wake Field Accelerator has a higher efficiency and a lower total energy for the driving beam. Finally, we show for the Plasma Wake Field Accelerator that one can accelerate high quality low emittance beams and, in principle, obtain efficiencies and energy spreads comparable to those obtained with conventional techniques.

  14. Cerebral amyloid angiopathy

    MedlinePlus

    ... Fenichel GM, Jankovic J, Mazziotta JC, eds. Bradley's Neurology in Clinical Practice . 6th ed. Philadelphia, PA: Elsevier ... al. Course of cerebral amyloid angiopathy-related inflammation. Neurology. 2007;68:1411-1416. PMID: 17452586 www.ncbi. ...

  15. Rehabilitation in cerebral palsy.

    PubMed Central

    Molnar, G. E.

    1991-01-01

    Cerebral palsy is the most frequent physical disability of childhood onset. Over the past four decades, prevalence has remained remarkably constant at 2 to 3 per 1,000 live births in industrialized countries. In this article I concentrate on the rehabilitation and outcome of patients with cerebral palsy. The epidemiologic, pathogenetic, and diagnostic aspects are highlighted briefly as they pertain to the planning and implementation of the rehabilitation process. PMID:1866952

  16. Nanomedicine in cerebral palsy

    PubMed Central

    Balakrishnan, Bindu; Nance, Elizabeth; Johnston, Michael V; Kannan, Rangaramanujam; Kannan, Sujatha

    2013-01-01

    Cerebral palsy is a chronic childhood disorder that can have diverse etiologies. Injury to the developing brain that occurs either in utero or soon after birth can result in the motor, sensory, and cognitive deficits seen in cerebral palsy. Although the etiologies for cerebral palsy are variable, neuroinflammation plays a key role in the pathophysiology of the brain injury irrespective of the etiology. Currently, there is no effective cure for cerebral palsy. Nanomedicine offers a new frontier in the development of therapies for prevention and treatment of brain injury resulting in cerebral palsy. Nanomaterials such as dendrimers provide opportunities for the targeted delivery of multiple drugs that can mitigate several pathways involved in injury and can be delivered specifically to the cells that are responsible for neuroinflammation and injury. These materials also offer the opportunity to deliver agents that would promote repair and regeneration in the brain, resulting not only in attenuation of injury, but also enabling normal growth. In this review, the current advances in nanotechnology for treatment of brain injury are discussed with specific relevance to cerebral palsy. Future directions that would facilitate clinical translation in neonates and children are also addressed. PMID:24204146

  17. Cerebral Amyloid Angiopathy: Emerging Concepts

    PubMed Central

    2015-01-01

    Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid β-protein (Aβ)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Aβ deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies). CAA-associated vasculopathies lead to development of hemorrhagic lesions [lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis (cSS)/focal convexity subarachnoid hemorrhage (SAH)], ischemic lesions (cortical infarction and ischemic changes of the white matter), and encephalopathies that include subacute leukoencephalopathy caused by CAA-associated inflammation/angiitis. Thus, CAA is related to dementia, stroke, and encephalopathies. Recent advances in diagnostic procedures, particularly neuroimaging, have enabled us to establish a clinical diagnosis of CAA without brain biopsies. Sensitive magnetic resonance imaging (MRI) methods, such as gradient-echo T2* imaging and susceptibility-weighted imaging, are useful for detecting cortical microhemorrhages and cSS. Amyloid imaging with amyloid-binding positron emission tomography (PET) ligands, such as Pittsburgh Compound B, can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. In addition, cerebrospinal fluid markers may be useful, including levels of Aβ40 for CAA and anti-Aβ antibody for CAA-related inflammation. Moreover, cSS is closely associated with transient focal neurological episodes (TFNE). CAA-related inflammation/angiitis shares pathophysiology with amyloid-related imaging abnormalities (ARIA) induced by Aβ immunotherapies in AD patients. This article reviews CAA and CAA-related disorders with respect to their epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis

  18. Perinatal White Matter Injury: The Changing Spectrum of Pathology and Emerging Insights into Pathogenetic Mechanisms

    ERIC Educational Resources Information Center

    Back, Stephen A.

    2006-01-01

    Perinatal brain injury in survivors of premature birth has a unique and unexplained predilection for periventricular cerebral white matter. Periventricular white-matter injury (PWMI) is now the most common cause of brain injury in preterm infants and the leading cause of chronic neurological morbidity. The spectrum of chronic PWMI includes focal…

  19. The human cerebral cortex flattens during adolescence.

    PubMed

    Alemán-Gómez, Yasser; Janssen, Joost; Schnack, Hugo; Balaban, Evan; Pina-Camacho, Laura; Alfaro-Almagro, Fidel; Castro-Fornieles, Josefina; Otero, Soraya; Baeza, Immaculada; Moreno, Dolores; Bargalló, Nuria; Parellada, Mara; Arango, Celso; Desco, Manuel

    2013-09-18

    The human cerebral cortex appears to shrink during adolescence. To delineate the dynamic morphological changes involved in this process, 52 healthy male and female adolescents (11-17 years old) were neuroimaged twice using magnetic resonance imaging, approximately 2 years apart. Using a novel morphometric analysis procedure combining the FreeSurfer and BrainVisa image software suites, we quantified global and lobar change in cortical thickness, outer surface area, the gyrification index, the average Euclidean distance between opposing sides of the white matter surface (gyral white matter thickness), the convex ("exposed") part of the outer cortical surface (hull surface area), sulcal length, depth, and width. We found that the cortical surface flattens during adolescence. Flattening was strongest in the frontal and occipital cortices, in which significant sulcal widening and decreased sulcal depth co-occurred. Globally, sulcal widening was associated with cortical thinning and, for the frontal cortex, with loss of surface area. For the other cortical lobes, thinning was related to gyral white matter expansion. The overall flattening of the macrostructural three-dimensional architecture of the human cortex during adolescence thus involves changes in gray matter and effects of the maturation of white matter. PMID:24048830

  20. Vasospasm in Cerebral Inflammation

    PubMed Central

    Eisenhut, Michael

    2014-01-01

    All forms of cerebral inflammation as found in bacterial meningitis, cerebral malaria, brain injury, and subarachnoid haemorrhage have been associated with vasospasm of cerebral arteries and arterioles. Vasospasm has been associated with permanent neurological deficits and death in subarachnoid haemorrhage and bacterial meningitis. Increased levels of interleukin-1 may be involved in vasospasm through calcium dependent and independent activation of the myosin light chain kinase and release of the vasoconstrictor endothelin-1. Another key factor in the pathogenesis of cerebral arterial vasospasm may be the reduced bioavailability of the vasodilator nitric oxide. Therapeutic trials in vasospasm related to inflammation in subarachnoid haemorrhage in humans showed a reduction of vasospasm through calcium antagonists, endothelin receptor antagonists, statins, and plasminogen activators. Combination of therapeutic modalities addressing calcium dependent and independent vasospasm, the underlying inflammation, and depletion of nitric oxide simultaneously merit further study in all conditions with cerebral inflammation in double blind randomised placebo controlled trials. Auxiliary treatment with these agents may be able to reduce ischemic brain injury associated with neurological deficits and increased mortality. PMID:25610703

  1. Cerebral venous sinus thrombosis

    PubMed Central

    Allroggen, H.; Abbott, R.

    2000-01-01

    Cerebral venous sinus thrombosis is a challenging condition because of its variability of clinical symptoms and signs. It is very often unrecognised at initial presentation. All age groups can be affected. Large sinuses such as the superior sagittal sinus are most frequently involved. Extensive collateral circulation within the cerebral venous system allows for a significant degree of compensation in the early stages of thrombus formation. Systemic inflammatory diseases and inherited as well as acquired coagulation disorders are frequent causes, although in up to 30% of cases no underlying cause can be identified. The oral contraceptive pill appears to be an important additional risk factor. The spectrum of clinical presentations ranges from headache with papilloedema to focal deficit, seizures and coma. Magnetic resonance imaging with venography is the investigation of choice; computed tomography alone will miss a significant number of cases. It has now been conclusively shown that intravenous heparin is the first-line treatment for cerebral venous sinus thrombosis because of its efficacy, safety and feasability. Local thrombolysis may be indicated in cases of deterioration, despite adequate heparinisation. This should be followed by oral anticoagulation for 3-6 months. The prognosis of cerebral venous sinus thrombosis is generally favourable. A high index of clinical suspicion is needed to diagnose this uncommon condition so that appropriate treatment can be initiated.


Keywords: cerebral venous sinus thrombosis PMID:10622773

  2. Whites Trashing Whites: Multiculturalism's Liberal Guilt Trip.

    ERIC Educational Resources Information Center

    Holden, Michael

    1995-01-01

    Presents the opinions of a white, male literature professor who attended a conference of college writing teachers and was distressed because the overwhelmingly white audience listened quietly as speakers used the platform to identify whites as oppressors of minorities and linguistic imperialists. The paper questions the view that Standard English…

  3. Contrast-enhanced imaging of cerebral vasculature with laser speckle

    NASA Astrophysics Data System (ADS)

    Murari, K.; Li, N.; Rege, A.; Jia, X.; All, A.; Thakor, N.

    2007-08-01

    High-resolution cerebral vasculature imaging has applications ranging from intraoperative procedures to basic neuroscience research. Laser speckle, with spatial contrast processing, has recently been used to map cerebral blood flow. We present an application of the technique using temporal contrast processing to image cerebral vascular structures with a field of view a few millimeters across and approximately 20 μm resolution through a thinned skull. We validate the images using fluorescent imaging and demonstrate a factor of 2-4 enhancement in contrast-to-noise ratios over reflectance imaging using white or spectrally filtered green light. The contrast enhancement enables the perception of approximately 10%-30% more vascular structures without the introduction of any contrast agent.

  4. Cerebral amyloid angiopathy-related inflammation: an emerging disease.

    PubMed

    Savoiardo, M; Erbetta, A; Di Francesco, J C; Brioschi, M; Silani, V; Falini, A; Storchi, G; Brighina, L; Ferrarese, C; Ticozzi, N; Messina, S; Girotti, F

    2011-05-15

    Three elderly patients with, respectively: mild cognitive impairment, severe and progressive neurologic involvement, and focal neurologic deficit, were observed. MRI showed multiple areas of white matter edema, at times partially involving the cortex, in the first two patients, and a single area in the third. Treatment with steroids determined the disappearance of the lesions and clinical amelioration. The key to the diagnosis of cerebral amyloid angiopathy-related inflammation (CAA-ri) was the demonstration, with appropriate MRI sequences, of microbleeds consistent with cerebral amyloid angiopathy (CAA). This diagnosis was supported by genetic analysis of APOE with demonstration of ε4/ε4 genotype, found in about 80% of CAA patients who develop inflammatory changes. In the appropriate clinical setting, MRI demonstration of microbleeds supported by results of genetic analysis of APOE may strongly support the diagnosis of CAA-ri thus avoiding cerebral biopsy. PMID:24059616

  5. Neuroprotection after cerebral ischemia

    PubMed Central

    Namura, Shobu; Ooboshi, Hiroaki; Liu, Jialing; Yenari, Midori A.

    2013-01-01

    Cerebral ischemia, a focal or global insufficiency of blood flow to the brain, can arise through multiple mechanisms, including thrombosis and arterial hemorrhage. Ischemia is a major driver of stroke, one of the leading causes of morbidity and mortality worldwide. While the general etiology of cerebral ischemia and stroke has been known for some time, the conditions have only recently been considered treatable. This report describes current research in this field seeking to fully understand the pathomechanisms underlying stroke; to characterize the brain’s intrinsic injury, survival, and repair mechanisms; to identify putative drug targets as well as cell-based therapies; and to optimize the delivery of therapeutic agents to the damaged cerebral tissue. PMID:23488559

  6. Cerebral thrombosis and myeloproliferative neoplasms.

    PubMed

    Artoni, Andrea; Bucciarelli, Paolo; Martinelli, Ida

    2014-11-01

    Myeloproliferative neoplasms (MPN) are acquired clonal disorders characterized by the proliferation of bone marrow myeloid cells. Different somatic mutations have been recently associated with MPN, the most common being JAK-2 V617F. Among MPN, polycythemia vera and essential thrombocythemia are particularly associated with an increased risk to develop thrombotic complications, either arterial or venous. Cerebrovascular events (stroke and transient ischemic attacks) are prevalent, accounting for approximately two-thirds of all events. Also cerebral vein thrombosis can complicate MPN and can be the first manifestation of the disease. Risk factors for thrombosis in patients with MPN are related or unrelated to the disease. Among the former there are cellular risk factors, such as increased white blood cell counts, vascular cell activation, endothelial dysfunction, and plasmatic risk factors, such as increased plasma viscosity, reduced levels of protein S, increased thrombin generation. The latter include increased age and previous thrombotic events. In addition, common cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) contribute to the pathogenesis of arterial events, whereas circumstantial risk factors (particularly oral contraceptive use and pregnancy/puerperium) to that of venous events. Primary prevention of arterial thrombosis with antiplatelet therapy is warranted in the majority of patients with MPN, whereas primary prevention of venous thrombosis is limited to anticoagulant prophylaxis during high-risk situations. Secondary prevention includes long-term antiplatelet therapy for arterial and short- or long-term anticoagulant therapy for venous thrombosis, depending on the risk factors present at the first event. PMID:25217248

  7. Brainstem Involvement as a Cause of Central Sleep Apnea: Pattern of Microstructural Cerebral Damage in Patients with Cerebral Microangiopathy

    PubMed Central

    Duning, Thomas; Deppe, Michael; Brand, Eva; Stypmann, Jörg; Becht, Charlotte; Heidbreder, Anna; Young, Peter

    2013-01-01

    Background The exact underlying pathomechanism of central sleep apnea with Cheyne-Stokes respiration (CSA-CSR) is still unclear. Recent studies have demonstrated an association between cerebral white matter changes and CSA. A dysfunction of central respiratory control centers in the brainstem was suggested by some authors. Novel MR-imaging analysis tools now allow far more subtle assessment of microstructural cerebral changes. The aim of this study was to investigate whether and what severity of subtle structural cerebral changes could lead to CSA-CSR, and whether there is a specific pattern of neurodegenerative changes that cause CSR. Therefore, we examined patients with Fabry disease (FD), an inherited, lysosomal storage disease. White matter lesions are early and frequent findings in FD. Thus, FD can serve as a "model disease" of cerebral microangiopathy to study in more detail the impact of cerebral lesions on central sleep apnea. Patients and Methods Genetically proven FD patients (n = 23) and age-matched healthy controls (n = 44) underwent a cardio-respiratory polysomnography and brain MRI at 3.0 Tesla. We applied different MR-imaging techniques, ranging from semiquantitative measurement of white matter lesion (WML) volumes and automated calculation of brain tissue volumes to VBM of gray matter and voxel-based diffusion tensor imaging (DTI) analysis. Results In 5 of 23 Fabry patients (22%) CSA-CSR was detected. Voxel-based DTI analysis revealed widespread structural changes in FD patients when compared to the healthy controls. When calculated as a separate group, DTI changes of CSA-CSR patients were most prominent in the brainstem. Voxel-based regression analysis revealed a significant association between CSR severity and microstructural DTI changes within the brainstem. Conclusion Subtle microstructural changes in the brainstem might be a neuroanatomical correlate of CSA-CSR in patients at risk of WML. DTI is more sensitive and specific than

  8. Neuroprotective effects of systemic cerebral endothelial cell transplantation in a rat model of cerebral ischemia

    PubMed Central

    Moon, Jong-Hyun; Na, Joo-Young; Lee, Min-Cheol; Choi, Kang-Ho; Lee, Jeong-Kil; Min, Jung-Joon; Kim, Kyung-Tae; Park, Jong-Tae; Park, Man-Seok; Kim, Hyung-Seok

    2016-01-01

    Human cerebral microvascular endothelial cell line (hCMEC)/D3 cells, which are from a stable clonal cell line of human immortalized cerebral endothelial cells, were intra-arterially transplanted through the common carotid artery in a rat model of photochemical-induced cerebral ischemia. Their therapeutic effects on infarct size, blood-brain barrier (BBB) breakdown, and outcome were examined. The hCMEC/D3 cells were genetically modified with the firefly luciferase gene for in vivo imaging post-transplantation. Transplanted hCMEC/D3 cells were identified in the infarcted brain by bioluminescence imaging at 1 day after transplantation. Compared with the control group, the hCMEC/D3-transplanted group showed reduced infarct size on day 3, reduced Evans blue dye leakage on day 1 indicating decreased BBB breakdown, and early recovery from Rotarod test neurological deficits. The hCMEC/D3-transplanted group also showed decreased levels of matrix metalloproteinase (MMP)-9, which were inversely correlated with TIMP-1 levels on post-transplantation days 1 and 3. The expression of tumor necrosis factor-α and interleukin-1β were markedly diminished in the hCMEC/D3-transplanted group compared with controls. The systemically transplanted cells selectively migrated and integrated into the ischemically lesioned area, which accelerated neurological recovery. This new cerebral endothelial cell-based therapy may hold promise for clinical trials in patients with ischemic stroke. PMID:27347342

  9. Neuroprotective effects of systemic cerebral endothelial cell transplantation in a rat model of cerebral ischemia.

    PubMed

    Moon, Jong-Hyun; Na, Joo-Young; Lee, Min-Cheol; Choi, Kang-Ho; Lee, Jeong-Kil; Min, Jung-Joon; Kim, Kyung-Tae; Park, Jong-Tae; Park, Man-Seok; Kim, Hyung-Seok

    2016-01-01

    Human cerebral microvascular endothelial cell line (hCMEC)/D3 cells, which are from a stable clonal cell line of human immortalized cerebral endothelial cells, were intra-arterially transplanted through the common carotid artery in a rat model of photochemical-induced cerebral ischemia. Their therapeutic effects on infarct size, blood-brain barrier (BBB) breakdown, and outcome were examined. The hCMEC/D3 cells were genetically modified with the firefly luciferase gene for in vivo imaging post-transplantation. Transplanted hCMEC/D3 cells were identified in the infarcted brain by bioluminescence imaging at 1 day after transplantation. Compared with the control group, the hCMEC/D3-transplanted group showed reduced infarct size on day 3, reduced Evans blue dye leakage on day 1 indicating decreased BBB breakdown, and early recovery from Rotarod test neurological deficits. The hCMEC/D3-transplanted group also showed decreased levels of matrix metalloproteinase (MMP)-9, which were inversely correlated with TIMP-1 levels on post-transplantation days 1 and 3. The expression of tumor necrosis factor-α and interleukin-1β were markedly diminished in the hCMEC/D3-transplanted group compared with controls. The systemically transplanted cells selectively migrated and integrated into the ischemically lesioned area, which accelerated neurological recovery. This new cerebral endothelial cell-based therapy may hold promise for clinical trials in patients with ischemic stroke. PMID:27347342

  10. The fetal cerebral circulation: three decades of exploration by the LLU Center for Perinatal Biology.

    PubMed

    Pearce, William J

    2014-01-01

    For more than three decades, research programs in the Center of Perinatal Biology have focused on the vascular biology of the fetal cerebral circulation. In the 1980s, research in the Center demonstrated that cerebral autoregulation operated over a narrower pressure range, and was more vulnerable to insults, in fetuses than in adults. Other studies were among the first to establish that compared to adult cerebral arteries, fetal cerebral arteries were more hydrated, contained smaller smooth muscle cells and less connective tissue, and had endothelium less capable of producing NO. Work in the 1990s revealed that pregnancy depressed reactivity to NO in extra-cerebral arteries, but elevated it in cerebral arteries through effects involving changes in cGMP metabolism. Comparative studies verified that fetal lamb cerebral arteries were an excellent model for cerebral arteries from human infants. Biochemical studies demonstrated that cGMP metabolism was dramatically upregulated, but that contraction was far more dependent on calcium influx, in fetal compared to adult cerebral arteries. Further studies established that chronic hypoxia accelerates functional maturation of fetal cerebral arteries, as indicated by increased contractile responses to adrenergic agonists and perivascular adrenergic nerves. In the 2000s, studies of signal transduction established age-dependent roles for PKG, PKC, PKA, ERK, ODC, IP3, myofilament calcium sensitivity, and many other mechanisms. These diverse studies clearly demonstrated that fetal cerebral arteries were functionally quite distinct compared to adult cerebral arteries. In the current decade, research in the Center has expanded to a more molecular focus on epigenetic mechanisms and their role in fetal vascular adaptation to chronic hypoxia, maternal drug abuse, and nutrient deprivation. Overall, the past three decades have transformed thinking about, and understanding of, the fetal cerebral circulation due in no small part to the

  11. Cerebral Folate Deficiency

    ERIC Educational Resources Information Center

    Gordon, Neil

    2009-01-01

    Cerebral folate deficiency (CFD) is associated with low levels of 5-methyltetrahydrofolate in the cerebrospinal fluid (CSF) with normal folate levels in the plasma and red blood cells. The onset of symptoms caused by the deficiency of folates in the brain is at around 4 to 6 months of age. This is followed by delayed development, with deceleration…

  12. Cerebral Palsy Litigation

    PubMed Central

    Sartwelle, Thomas P.

    2015-01-01

    The cardinal driver of cerebral palsy litigation is electronic fetal monitoring, which has continued unabated for 40 years. Electronic fetal monitoring, however, is based on 19th-century childbirth myths, a virtually nonexistent scientific foundation, and has a false positive rate exceeding 99%. It has not affected the incidence of cerebral palsy. Electronic fetal monitoring has, however, increased the cesarian section rate, with the expected increase in mortality and morbidity risks to mothers and babies alike. This article explains why electronic fetal monitoring remains endorsed as efficacious in the worlds’ labor rooms and courtrooms despite being such a feeble medical modality. It also reviews the reasons professional organizations have failed to condemn the use of electronic fetal monitoring in courtrooms. The failures of tort reform, special cerebral palsy courts, and damage limits to stem the escalating litigation are discussed. Finally, the authors propose using a currently available evidence rule—the Daubert doctrine that excludes “junk science” from the courtroom—as the beginning of the end to cerebral palsy litigation and electronic fetal monitoring’s 40-year masquerade as science. PMID:25183322

  13. Cerebral Palsy Among Asian Ethnic Subgroups

    PubMed Central

    Lang, Tess C.; Fuentes-Afflick, Elena; Gilbert, William M.; Newman, Thomas B.; Xing, Guibo

    2012-01-01

    OBJECTIVE: Asians have a reduced risk for cerebral palsy (CP) compared with whites. We examined whether individual Asian subgroups have a reduced risk of CP and whether differences in sociodemographic factors explain disparities in CP prevalence. METHODS: In a retrospective cohort of 629 542 Asian and 2 109 550 white births in California from 1991 to 2001, we identified all children who qualified for services from the California Department of Health Services on the basis of CP. Asians were categorized as East Asian (Chinese, Japanese, Koreans), Filipino, Indian, Pacific Islander (Guamanians, Hawaiians, and Pacific Islanders), Samoan, or Southeast Asian (Cambodian, Laotian, Thai, Vietnamese). RESULTS: Overall, CP prevalence was lower in Asians than whites (1.09 vs 1.36 per 1000; relative risk = 0.80, 95% confidence interval [CI] = 0.74–0.87) and ranged from 0.61/1000 in Thai children to 2.08/1000 in Samoan children. Several Asian subgroups had low risk profiles with respect to maternal age, educational attainment, and birth weight. However, after we adjusted for maternal age and education, infant gender, and birth weight, the adjusted risk of CP remained lower in East Asians (odds ratio [OR] = 0.75, 95% CI = 0.65–0.87), Filipinos (OR = 0.87, 95% CI = 0.75–0.99), Indians (OR = 0.59, 95% CI = 0.44–0.80), Pacific Islanders (OR = 0.62, 95% CI = 0.40–0.97), and Southeast Asians (OR = 0.68, 95% CI = 0.57–0.82) compared with whites. CONCLUSIONS: Most Asian national origin subgroups have a lower rate of CP than whites, and this disparity is unexplained. Additional studies that focus on the cause of ethnic disparities in CP may provide new insights into pathogenesis and prevention. PMID:22430449

  14. Increased Cerebral Water Content in Hemodialysis Patients

    PubMed Central

    Costa, Ana Sofia; Gras, Vincent; Tiffin-Richards, Frances; Mirzazade, Shahram; Holschbach, Bernhard; Frank, Rolf Dario; Vassiliadou, Athina; Krüger, Thilo; Eitner, Frank; Gross, Theresa; Schulz, Jörg Bernhard; Floege, Jürgen; Shah, Nadim Jon

    2015-01-01

    Little information is available on the impact of hemodialysis on cerebral water homeostasis and its distribution in chronic kidney disease. We used a neuropsychological test battery, structural magnetic resonance imaging (MRI) and a novel technique for quantitative measurement of localized water content using 3T MRI to investigate ten hemodialysis patients (HD) on a dialysis-free day and after hemodialysis (2.4±2.2 hours), and a matched healthy control group with the same time interval. Neuropsychological testing revealed mainly attentional and executive cognitive dysfunction in HD. Voxel-based-morphometry showed only marginal alterations in the right inferior medial temporal lobe white matter in HD compared to controls. Marked increases in global brain water content were found in the white matter, specifically in parietal areas, in HD patients compared to controls. Although the global water content in the gray matter did not differ between the two groups, regional increases of brain water content in particular in parieto-temporal gray matter areas were observed in HD patients. No relevant brain hydration changes were revealed before and after hemodialysis. Whereas longer duration of dialysis vintage was associated with increased water content in parieto-temporal-occipital regions, lower intradialytic weight changes were negatively correlated with brain water content in these areas in HD patients. Worse cognitive performance on an attention task correlated with increased hydration in frontal white matter. In conclusion, long-term HD is associated with altered brain tissue water homeostasis mainly in parietal white matter regions, whereas the attentional domain in the cognitive dysfunction profile in HD could be linked to increased frontal white matter water content. PMID:25826269

  15. A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice.

    PubMed

    Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Haast, Roy; Lütjohann, Dieter; Broersen, Laus M; Heerschap, Arend; Kiliaan, Amanda J

    2016-01-01

    APOE ε4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10-12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16-18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging. PMID:27034849

  16. A Dietary Treatment Improves Cerebral Blood Flow and Brain Connectivity in Aging apoE4 Mice

    PubMed Central

    Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Haast, Roy; Lütjohann, Dieter; Broersen, Laus M.; Heerschap, Arend

    2016-01-01

    APOE ε4 (apoE4) polymorphism is the main genetic determinant of sporadic Alzheimer's disease (AD). A dietary approach (Fortasyn) including docosahexaenoic acid, eicosapentaenoic acid, uridine, choline, phospholipids, folic acid, vitamins B12, B6, C, and E, and selenium has been proposed for dietary management of AD. We hypothesize that the diet could inhibit AD-like pathologies in apoE4 mice, specifically cerebrovascular and connectivity impairment. Moreover, we evaluated the diet effect on cerebral blood flow (CBF), functional connectivity (FC), gray/white matter integrity, and postsynaptic density in aging apoE4 mice. At 10–12 months, apoE4 mice did not display prominent pathological differences compared to wild-type (WT) mice. However, 16–18-month-old apoE4 mice revealed reduced CBF and accelerated synaptic loss. The diet increased cortical CBF and amount of synapses and improved white matter integrity and FC in both aging apoE4 and WT mice. We demonstrated that protective mechanisms on vascular and synapse health are enhanced by Fortasyn, independent of apoE genotype. We further showed the efficacy of a multimodal translational approach, including advanced MR neuroimaging, to study dietary intervention on brain structure and function in aging. PMID:27034849

  17. Role of phorbol esters in regional cerebral blood flow regulation

    SciTech Connect

    Hanley, D.F.; Uhl, G.R.; Miyabe, M.; Traystman, R.J.

    1986-03-05

    Phorbol esters are known to activate protein kinase C, an intracellular enzyme capable of phosphorylating membrane associated receptors. By using phorbol-12-13-dibutyrate (PDBU), they investigated the presence and function of protein kinase C on canine cerebral vessels. In vitro tissue autoradiographic studies performed on 8 ..mu.. sections of canine cerebral vessels with H/sup 3/-PDBU revealed a 3 to 1 ratio of specific to nonspecific binding. Competitive displacement was demonstrated for 3 physiologically active phorbol esters but could not be demonstrated for 3 physiologically inactive phorbol derivatives. The effect of PDBU on regional cerebral blood flow (rCBF) was then studied in vivo using radiolabelled microspheres in 6 dogs. Measurements were made during control ventriculocisternal CSF infusions and 5,10,15,20 and 25 minutes after infusion of .1 nM/min PDBU. For grey matter regions in contact with the perfusate, caudate nucleus, cortical watershed and cerebellum, blood flow increased from 33 +/- 6 to 45 +/- 7, 20 +/- 2 to 27 +/- 2, and 31 +/- 2 to 42 +/- 5 ml/min/100 gm, respectively. rCBF was unchanged for brainstem, temporal lobe or white matter regions. They conclude (1) PDBU has high affinity binding to canine cerebral vascular smooth muscle, and (2) PDBU produces an increase in rCBF when delivered intraventricularly. These data suggest a possible role for protein kinase C in the regulation of cerebral blood flow.

  18. Accelerated Reader.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    This paper provides an overview of Accelerated Reader, a system of computerized testing and record-keeping that supplements the regular classroom reading program. Accelerated Reader's primary goal is to increase literature-based reading practice. The program offers a computer-aided reading comprehension and management program intended to motivate…

  19. Is Vasomotion in Cerebral Arteries Impaired in Alzheimer's Disease?

    PubMed

    Di Marco, Luigi Yuri; Farkas, Eszter; Martin, Chris; Venneri, Annalena; Frangi, Alejandro F

    2015-01-01

    A substantial body of evidence supports the hypothesis of a vascular component in the pathogenesis of Alzheimer's disease (AD). Cerebral hypoperfusion and blood-brain barrier dysfunction have been indicated as key elements of this pathway. Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder, frequent in AD, characterized by the accumulation of amyloid-β (Aβ) peptide in cerebral blood vessel walls. CAA is associated with loss of vascular integrity, resulting in impaired regulation of cerebral circulation, and increased susceptibility to cerebral ischemia, microhemorrhages, and white matter damage. Vasomotion- the spontaneous rhythmic modulation of arterial diameter, typically observed in arteries/arterioles in various vascular beds including the brain- is thought to participate in tissue perfusion and oxygen delivery regulation. Vasomotion is impaired in adverse conditions such as hypoperfusion and hypoxia. The perivascular and glymphatic pathways of Aβ clearance are thought to be driven by the systolic pulse. Vasomotion produces diameter changes of comparable amplitude, however at lower rates, and could contribute to these mechanisms of Aβ clearance. In spite of potential clinical interest, studies addressing cerebral vasomotion in the context of AD/CAA are limited. This study reviews the current literature on vasomotion, and hypothesizes potential paths implicating impaired cerebral vasomotion in AD/CAA. Aβ and oxidative stress cause vascular tone dysregulation through direct effects on vascular cells, and indirect effects mediated by impaired neurovascular coupling. Vascular tone dysregulation is further aggravated by cholinergic deficit and results in depressed cerebrovascular reactivity and (possibly) impaired vasomotion, aggravating regional hypoperfusion and promoting further Aβ and oxidative stress accumulation. PMID:25720414

  20. Biofidelic white matter heterogeneity decreases computational model predictions of white matter strains during rapid head rotations.

    PubMed

    Maltese, Matthew R; Margulies, Susan S

    2016-11-01

    The finite element (FE) brain model is used increasingly as a design tool for developing technology to mitigate traumatic brain injury. We developed an ultra high-definition FE brain model (>4 million elements) from CT and MRI scans of a 2-month-old pre-adolescent piglet brain, and simulated rapid head rotations. Strain distributions in the thalamus, coronal radiata, corpus callosum, cerebral cortex gray matter, brainstem and cerebellum were evaluated to determine the influence of employing homogeneous brain moduli, or distinct experimentally derived gray and white matter property representations, where some white matter regions are stiffer and others less stiff than gray matter. We find that constitutive heterogeneity significantly lowers white matter deformations in all regions compared with homogeneous properties, and should be incorporated in FE model injury prediction. PMID:27123826

  1. Cerebral Ischemia Mediates the Effect of Serum Uric Acid on Cognitive Function

    PubMed Central

    Vannorsdall, Tracy D.; Jinnah, H.A.; Gordon, Barry; Kraut, Michael; Schretlen, David J.

    2016-01-01

    Background and Purpose High normal concentrations of serum uric acid (UA) are associated with mild cognitive dysfunction and increased cerebral ischemia as indexed by white matter hyperintensity volumes. We hypothesized that individual differences in white matter hyperintensities mediate the association between UA and mild cognitive dysfunction. Methods One hundred eighty community-dwelling adults aged 20 to 96 years completed neuropsychological testing, laboratory blood studies, and a brain MRI scan. Results Serum UA was associated (P<0.05) with greater white matter hyperintensities and poorer working memory, processing speed, fluency, and verbal memory. Associations remained after controlling for age, sex, race, education, hypertension, diabetes, alcohol abuse, smoking, and body mass. Adding a term for white matter hyperintensity attenuated these associations such that UA no longer predicted cognitive performance. Conclusions Severity of cerebral ischemia might mediate the association between UA and cognitive dysfunction. Even mild elevations in UA appear to contribute to structural and functional brain changes. PMID:18772442

  2. Early CT findings of acute cerebral infarction in the middle cerebral artery territory.

    PubMed

    Ying, K S; Pang, K K; Huang, J K; Lin, J C

    1992-04-01

    For an early and definitive diagnosis of acute cerebral infarction by computed tomography (CT), we retrospectively analyzed the initial CT findings of 14 patients with proven acute middle cerebral artery (MCA) infarction within 4 hours after stroke onset. The following results were obtained: (a) abnormal CT findings could be recognized quite early in 13 patients (92.9%), (b) the most common and earliest finding was loss of defination of the gray-white interface at the lateral margins of the insula. This sign was recognized in 12 patients (85.7%) and could be detected as early as 1 hour after stroke onset, (c) the next common finding was narrowing or blurring of the Sylvian fissure in 10 patients (71.4%) and could be detected 1.5 hours after stroke onset, (d) an obscured outline or partial disappearance of the lentiform nucleus was recognized in 7 patients (50%) and could be detected 1.5 hours after stroke onset, (e) effacement of the cerebral sulci was found in 6 patients (42.9%) and could be detected 2.5 hours after stroke onset, (f) increased density in MCA or its major branches was not seen in our patients. PMID:1318145

  3. Noninvasive measurement of cerebral oxygen saturation and cerebral phronetal function

    NASA Astrophysics Data System (ADS)

    Li, Shengli; Zhang, Aiyu; Xu, Min; Jin, Taiyi

    1998-08-01

    Using the Near-Infrared Spectroscopy (NIRS), the noninvasive measurement of cerebral oxygen concentration can be achieved in vivo based on the Lambert-Beer Law. In this paper, we discuss the possibility of studying higher brain functions through combining cerebral oxygen saturation and cerebral function measurement. Event-related experiments are introduced to measure the cerebral phronetal function. Time domain curves show sight differences among these experiment results. However, with the aid of DFT, experiment data of all five human volunteers show the frequency near 20 Hz or 40 Hz is evoked depending on the difficulty of the mental tasks. The results demonstrate the feasibility of cerebral functions study by means of cerebral oxygen saturation measurement analyzed in the frequency domain.

  4. LINEAR ACCELERATOR

    DOEpatents

    Colgate, S.A.

    1958-05-27

    An improvement is presented in linear accelerators for charged particles with respect to the stable focusing of the particle beam. The improvement consists of providing a radial electric field transverse to the accelerating electric fields and angularly introducing the beam of particles in the field. The results of the foregoing is to achieve a beam which spirals about the axis of the acceleration path. The combination of the electric fields and angular motion of the particles cooperate to provide a stable and focused particle beam.

  5. Aging White Matter and Cognition: Differential Effects of Regional Variations in Diffusion Properties on Memory, Executive Functions, and Speed

    ERIC Educational Resources Information Center

    Kennedy, Kristen M.; Raz, Naftali

    2009-01-01

    Disruption of cerebral white matter has been proposed as an explanation for age-related cognitive declines. However, the role of specific regions in specific cognitive declines remains unclear. We used diffusion tensor imaging to examine the associations between regional microstructural integrity of the white matter and performance on…

  6. Subcortical white matter abnormalities related to drug resistance in Wilson disease.

    PubMed

    Aikath, D; Gupta, A; Chattopadhyay, I; Hashmi, M A; Gangopadhyay, P K; Das, S K; Ray, K

    2006-09-12

    Wilson disease (WD) produces typical lesions in the brain, which can aid in diagnosis and therapy. The authors present a drug-resistant WD case with atypical cerebral lesions with marked involvement of white matter as visualized on MRI scans. The diagnosis was confirmed by identification of mutations in the ATP7B gene. The case demonstrates an uncommon pathology-related cerebral copper accumulation and emphasizes the importance of genetic screening in the diagnosis of WD. PMID:16966556

  7. Genetics of Cerebral Vasospasm

    PubMed Central

    Ladner, Travis R.; Zuckerman, Scott L.; Mocco, J

    2013-01-01

    Cerebral vasospasm (CV) is a major source of morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH). It is thought that an inflammatory cascade initiated by extravasated blood products precipitates CV, disrupting vascular smooth muscle cell function of major cerebral arteries, leading to vasoconstriction. Mechanisms of CV and modes of therapy are an active area of research. Understanding the genetic basis of CV holds promise for the recognition and treatment for this devastating neurovascular event. In our review, we summarize the most recent research involving key areas within the genetics and vasospasm discussion: (1) Prognostic role of genetics—risk stratification based on gene sequencing, biomarkers, and polymorphisms; (2) Signaling pathways—pinpointing key inflammatory molecules responsible for downstream cellular signaling and altering these mediators to provide therapeutic benefit; and (3) Gene therapy and gene delivery—using viral vectors or novel protein delivery methods to overexpress protective genes in the vasospasm cascade. PMID:23691311

  8. ION ACCELERATOR

    DOEpatents

    Bell, J.S.

    1959-09-15

    An arrangement for the drift tubes in a linear accelerator is described whereby each drift tube acts to shield the particles from the influence of the accelerating field and focuses the particles passing through the tube. In one embodiment the drift tube is splii longitudinally into quadrants supported along the axis of the accelerator by webs from a yoke, the quadrants. webs, and yoke being of magnetic material. A magnetic focusing action is produced by energizing a winding on each web to set up a magnetic field between adjacent quadrants. In the other embodiment the quadrants are electrically insulated from each other and have opposite polarity voltages on adjacent quadrants to provide an electric focusing fleld for the particles, with the quadrants spaced sufficienily close enough to shield the particles within the tube from the accelerating electric field.

  9. Acceleration switch

    DOEpatents

    Abbin, J.P. Jr.; Devaney, H.F.; Hake, L.W.

    1979-08-29

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  10. Acceleration switch

    DOEpatents

    Abbin, Jr., Joseph P.; Devaney, Howard F.; Hake, Lewis W.

    1982-08-17

    The disclosure relates to an improved integrating acceleration switch of the type having a mass suspended within a fluid filled chamber, with the motion of the mass initially opposed by a spring and subsequently not so opposed.

  11. Cerebral dysgenesis. An overview.

    PubMed

    Schaefer, G B; Sheth, R D; Bodensteiner, J B

    1994-11-01

    A significant portion of patients with neurodevelopmental abnormalities (mental retardation, learning disabilities, and so forth) have no definable cause for these problems. Mounting evidence suggests a substantial number of these idiopathic conditions have subtle abnormalities of brain development (cerebral dysgenesis) as the inherent pathophysiologic event. In this article the authors summarize normal and abnormal brain development, the diagnostic approach to idiopathic neurodevelopmental anomalies, and the new molecular genetic insights into the underlying causes of brain malformations. PMID:7845342

  12. Phenylpropanolamine and cerebral hemorrhage

    SciTech Connect

    McDowell, J.R.; LeBlanc, H.J.

    1985-05-01

    Computerized tomography, carotid angiograms, and arteriography were used to diagnose several cases of cerebral hemorrhage following the use of phenylpropanolamine. The angiographic picture in one of the three cases was similar to that previously described in association with amphetamine abuse and pseudoephedrine overdose, both substances being chemically and pharmacologically similar to phenylpropanolamine. The study suggests that the arterial change responsible for symptoms may be due to spasm rather than arteriopathy. 14 references, 5 figures.

  13. LINEAR ACCELERATOR

    DOEpatents

    Christofilos, N.C.; Polk, I.J.

    1959-02-17

    Improvements in linear particle accelerators are described. A drift tube system for a linear ion accelerator reduces gap capacity between adjacent drift tube ends. This is accomplished by reducing the ratio of the diameter of the drift tube to the diameter of the resonant cavity. Concentration of magnetic field intensity at the longitudinal midpoint of the external sunface of each drift tube is reduced by increasing the external drift tube diameter at the longitudinal center region.

  14. Cerebral autoregulation and brain networks in occlusive processes of the internal carotid artery

    PubMed Central

    Avirame, Keren; Lesemann, Anne; List, Jonathan; Witte, Anja Veronica; Schreiber, Stephan Joachim; Flöel, Agnes

    2015-01-01

    Patients with unilateral occlusive processes of the internal carotid artery (ICA) show subtle cognitive deficits. Decline in cerebral autoregulation and in functional and structural integrity of brain networks have previously been reported in the affected hemisphere (AH). However, the association between cerebral autoregulation, brain networks, and cognition remains to be elucidated. Fourteen neurologically asymptomatic patients (65±11 years) with either ICA occlusion or high-grade ICA stenosis and 11 age-matched healthy controls (HC) (67±6 years) received neuropsychologic testing, transcranial Doppler sonography to assess cerebral autoregulation using vasomotor reactivity (VMR), and magnetic resonance imaging to probe white matter microstructure and resting-state functional connectivity (RSFC). Patients performed worse on memory and executive tasks when compared with controls. Vasomotor reactivity, white matter microstructure, and RSFC were lower in the AH of the patients when compared with the unaffected hemisphere and with controls. Lower VMR of the AH was associated with several ipsilateral clusters of lower white matter microstructure and lower bilateral RSFC in patients. No correlations were found between VMR and cognitive scores. In sum, impaired cerebral autoregulation was associated with reduced structural and functional connectivity in cerebral networks, indicating possible mechanisms by which severe unilateral occlusive processes of the ICA lead to cognitive decline. PMID:25388676

  15. [Insomnia and cerebral hypoperfusion].

    PubMed

    Káposzta, Zoltán; Rácz, Klára

    2007-11-18

    Insomnia is defined as difficulty with the initiation, maintenance, duration, or quality of sleep that results in the impairment of daytime functioning, despite adequate opportunity and circumstances for sleep. In most countries approximately every third inhabitant has insomnia. Insomnia can be classified as primary and secondary. The pathogenesis of primary insomnia is unknown, but available evidence suggests a state of hyperarousal. Insomnia secondary to other causes is more common than primary insomnia. Cerebral hypoperfusion can be the cause of insomnia in some cases. In such patients the cerebral blood flow should be improved using parenteral vascular therapy. If insomnia persists despite treatment, then therapy for primary insomnia should be instituted using benzodiazepine-receptor agonists such as Zolpidem, Zopiclone, or Zaleplon. In those cases Midazolam cannot be used for the treatment of insomnia due to its marked negative effect on cerebral blood flow. In Hungary there is a need to organize multidisciplinary Insomnia Clinics because insomnia is more than a disease, it is a public health problem in this century. PMID:17988972

  16. Cerebral oxygenation and hyperthermia

    PubMed Central

    Bain, Anthony R.; Morrison, Shawnda A.; Ainslie, Philip N.

    2014-01-01

    Hyperthermia is associated with marked reductions in cerebral blood flow (CBF). Increased distribution of cardiac output to the periphery, increases in alveolar ventilation and resultant hypocapnia each contribute to the fall in CBF during passive hyperthermia; however, their relative contribution remains a point of contention, and probably depends on the experimental condition (e.g., posture and degree of hyperthermia). The hyperthermia-induced hyperventilatory response reduces arterial CO2 pressure (PaCO2) causing cerebral vasoconstriction and subsequent reductions in flow. During supine passive hyperthermia, the majority of recent data indicate that reductions in PaCO2 may be the primary, if not sole, culprit for reduced CBF. On the other hand, during more dynamic conditions (e.g., hemorrhage or orthostatic challenges), an inability to appropriately decrease peripheral vascular conductance presents a condition whereby adequate cerebral perfusion pressure may be compromised secondary to reductions in systemic blood pressure. Although studies have reported maintenance of pre-frontal cortex oxygenation (assessed by near-infrared spectroscopy) during exercise and severe heat stress, the influence of cutaneous blood flow is known to contaminate this measure. This review discusses the governing mechanisms associated with changes in CBF and oxygenation during moderate to severe (i.e., 1.0°C to 2.0°C increase in body core temperature) levels of hyperthermia. Future research directions are provided. PMID:24624095

  17. What provides cerebral reserve?

    PubMed

    Staff, Roger T; Murray, Alison D; Deary, Ian J; Whalley, Lawrence J

    2004-05-01

    The cerebral reserve hypothesis is a heuristic concept used to explain apparent protection from the onset of cerebral disease and/or cognitive decline in old age. A significant obstacle when investigating the reserve hypothesis is the absence of baseline data with which to compare current cognitive status. We tested the influence of three hypothesized proxies of reserve (education, head size and occupational attainment [OCC]) in 92 volunteers born in 1921, whose cognitive function was measured at age 11 and 79 years, and who underwent brain MRI. The association between each proxy and old age cognitive function was tested, adjusting for variance contributed by childhood mental ability and detrimental age-related pathological changes measured using MRI. The results showed that education and OCC, but not total intracranial volume (TICV), contribute to cerebral reserve and help retain cognitive function in old age. Education was found to contribute between 5 and 6% of the variance found in old age memory function but was found to have no significant association with reasoning abilities. OCC was found to contribute around 5% of the variance found in old age memory function and between 6 and 8% of the variance found in old age reasoning abilities. We conclude that the intellectual challenges experienced during life, such as education and occupation, accumulate reserve and allow cognitive function to be maintained in old age. PMID:15047587

  18. Unique Transcriptome Patterns of the White and Grey Matter Corroborate Structural and Functional Heterogeneity in the Human Frontal Lobe

    PubMed Central

    Mills, James D.; Kavanagh, Tomas; Kim, Woojin S.; Chen, Bei Jun; Kawahara, Yoshihiro; Halliday, Glenda M.; Janitz, Michael

    2013-01-01

    The human frontal lobe has undergone accelerated evolution, leading to the development of unique human features such as language and self-reflection. Cortical grey matter and underlying white matter reflect distinct cellular compositions in the frontal lobe. Surprisingly little is known about the transcriptomal landscape of these distinct regions. Here, for the first time, we report a detailed transcriptomal profile of the frontal grey (GM) and white matter (WM) with resolution to alternatively spliced isoforms obtained using the RNA-Seq approach. We observed more vigorous transcriptome activity in GM compared to WM, presumably because of the presence of cellular bodies of neurons in the GM and RNA associated with the nucleus and perinuclear space. Among the top differentially expressed genes, we also identified a number of long intergenic non-coding RNAs (lincRNAs), specifically expressed in white matter, such as LINC00162. Furthermore, along with confirmation of expression of known markers for neurons and oligodendrocytes, we identified a number of genes and splicing isoforms that are exclusively expressed in GM or WM with examples of GABRB2 and PAK2 transcripts, respectively. Pathway analysis identified distinct physiological and biochemical processes specific to grey and white matter samples with a prevalence of synaptic processes in GM and myelination regulation and axonogenesis in the WM. Our study also revealed that expression of many genes, for example, the GPR123, is characterized by isoform switching, depending in which structure the gene is expressed. Our report clearly shows that GM and WM have perhaps surprisingly divergent transcriptome profiles, reflecting distinct roles in brain physiology. Further, this study provides the first reference data set for a normal human frontal lobe, which will be useful in comparative transcriptome studies of cerebral disorders, in particular, neurodegenerative diseases. PMID:24194939

  19. Sympathetic regulation of cerebral blood flow during seizures in newborn lambs

    SciTech Connect

    Kurth, C.D.; Wagerle, L.C.; Delivoria-Papadopoulos, M. )

    1988-09-01

    The authors examined cerebral blood flow (CBF) regulation by the sympathetic nerves in 12 newborn lambs during seizures, a potent reflex stimulator of the sympathetic nervous system. CBF was measured with microspheres, and seizures were induced with bicuculline. In six of these lambs, one hemibrain was denervated (D) chronically by interrupting the ipsilateral cervical sympathetic trunk; the other hemibrain remained innervated (I). Before and after 10, 35, and 70 min of seizures, cerebral gray matter blood flow was measured. In the cerebral white matter, hippocampus, caudate, and thalamus blood flows to the D and I hemibrains were similar before seizures but during seizures they were 10-39% greater in the D than in the I hemibrain. Midbrain, brainstem, and cerebellum D and I blood flows were always similar. In the other six lambs, acute denervation during seizures increased ipsilateral cerebral gray and hippocampus blood flow by 10-31%, but unilateral electrical stimulation decreased ipsilateral cerebral gray, cerebral white, hippocampus, thalamus, and caudate blood flow by 17-27%. The data demonstrate that, during seizures, sympathetic nerve activity modifies regional CBF and the effect is sustained, suggesting a role for the sympathetic nervous system in newborn CBF regulation.

  20. What You Should Know about Cerebral Aneurysms

    MedlinePlus

    ... About Stroke What You Should Know About Cerebral Aneurysms Updated:Jun 13,2014 About Cerebral Aneurysms Diagnosis ... to view an animation What is a cerebral aneurysm? An aneurysm is a weak area in a ...

  1. Molecular pathophysiology of cerebral edema.

    PubMed

    Stokum, Jesse A; Gerzanich, Volodymyr; Simard, J Marc

    2016-03-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

  2. Molecular pathophysiology of cerebral edema

    PubMed Central

    Gerzanich, Volodymyr; Simard, J Marc

    2015-01-01

    Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

  3. Radiosurgery for cerebral arteriovenous malformations in hereditary hemorrhagic telangiectasia.

    PubMed

    Maarouf, M; Runge, M; Kocher, M; Zähringer, M; Treuer, H; Sturm, V

    2004-07-27

    The authors evaluated the efficacy of radiosurgery (RS) for cerebral arteriovenous malformations in hereditary hemorrhagic telangiectasia (HHT AVMs). Two patients with seven HHT AVMs were treated by linear accelerator-RS. Complete obliteration was achieved 18 to 24 months post-treatment without side effects. Because HHT AVMs are small and multiple, RS is superior to microsurgery because it is noninvasive and all AVMs can be treated in one session regardless of their location. PMID:15277641

  4. Confronting White Privilege

    ERIC Educational Resources Information Center

    Swalwell, Katy

    2012-01-01

    Even as the United States becomes more diverse, a new era of "white flight" is unfolding. Whether they live in urban, suburban or rural communities, white students are likely to attend schools that reinforce their perceptions of cultural dominance. The average white student attends a school where 77 percent of the student body is of their race.…

  5. White, Male, and "Minority": Racial Consciousness among White Male Undergraduates Attending a Historically Black University

    ERIC Educational Resources Information Center

    Peterson, R. Darrell; Hamrick, Florence A.

    2009-01-01

    Enrollments of non-Black students at historically Black colleges and universities (HBCUs) have recently increased to the point that 11% of all undergraduate students enrolled in HBCUs in 2001 were White (U. S. Department of Education National Center for Education Statistics [NCES], 2004). Accelerated transdemographic enrollment patterns (Brown) at…

  6. Cerebral magnetic resonance imaging of compressed air divers in diving accidents.

    PubMed

    Gao, G K; Wu, D; Yang, Y; Yu, T; Xue, J; Wang, X; Jiang, Y P

    2009-01-01

    To investigate the characteristics of the cerebral magnetic resonance imaging (MRI) of compressed air divers in diving accidents, we conducted an observational case series study. MRI of brain were examined and analysed on seven cases compressed air divers complicated with cerebral arterial gas embolism CAGE. There were some characteristics of cerebral injury: (1) Multiple lesions; (2) larger size; (3) Susceptible to parietal and frontal lobe; (4) Both cortical grey matter and subcortical white matter can be affected; (5) Cerebellum is also the target of air embolism. The MRI of brain is an sensitive method for detecting cerebral lesions in compressed air divers in diving accidents. The MRI should be finished on divers in diving accidents within 5 days. PMID:19341126

  7. Acceleration Studies

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.

    1993-01-01

    Work to support the NASA MSFC Acceleration Characterization and Analysis Project (ACAP) was performed. Four tasks (analysis development, analysis research, analysis documentation, and acceleration analysis) were addressed by parallel projects. Work concentrated on preparation for and implementation of near real-time SAMS data analysis during the USMP-1 mission. User support documents and case specific software documentation and tutorials were developed. Information and results were presented to microgravity users. ACAP computer facilities need to be fully implemented and networked, data resources must be cataloged and accessible, future microgravity missions must be coordinated, and continued Orbiter characterization is necessary.

  8. Pulsed arterial spin labeling effectively and dynamically observes changes in cerebral blood flow after mild traumatic brain injury

    PubMed Central

    Peng, Shu-ping; Li, Yi-ning; Liu, Jun; Wang, Zhi-yuan; Zhang, Zi-shu; Zhou, Shun-ke; Tao, Fang-xu; Zhang, Zhi-xue

    2016-01-01

    Cerebral blood flow is strongly associated with brain function, and is the main symptom and diagnostic basis for a variety of encephalopathies. However, changes in cerebral blood flow after mild traumatic brain injury remain poorly understood. This study sought to observe changes in cerebral blood flow in different regions after mild traumatic brain injury using pulsed arterial spin labeling. Our results demonstrate maximal cerebral blood flow in gray matter and minimal in the white matter of patients with mild traumatic brain injury. At the acute and subacute stages, cerebral blood flow was reduced in the occipital lobe, parietal lobe, central region, subcutaneous region, and frontal lobe. Cerebral blood flow was restored at the chronic stage. At the acute, subacute, and chronic stages, changes in cerebral blood flow were not apparent in the insula. Cerebral blood flow in the temporal lobe and limbic lobe diminished at the acute and subacute stages, but was restored at the chronic stage. These findings suggest that pulsed arterial spin labeling can precisely measure cerebral blood flow in various brain regions, and may play a reference role in evaluating a patient's condition and judging prognosis after traumatic brain injury. PMID:27073378

  9. Hemodynamics of Cerebral Aneurysms

    PubMed Central

    Sforza, Daniel M.; Putman, Christopher M.; Cebral, Juan Raul

    2009-01-01

    The initiation and progression of cerebral aneurysms are degenerative processes of the arterial wall driven by a complex interaction of biological and hemodynamic factors. Endothelial cells on the artery wall respond physiologically to blood-flow patterns. In normal conditions, these responses are associated with nonpathological tissue remodeling and adaptation. The combination of abnormal blood patterns and genetics predisposition could lead to the pathological formation of aneurysms. Here, we review recent progress on the basic mechanisms of aneurysm formation and evolution, with a focus on the role of hemodynamic patterns. PMID:19784385

  10. Cerebral involvement in axonal Charcot-Marie-Tooth neuropathy caused by mitofusin2 mutations.

    PubMed

    Brockmann, Knut; Dreha-Kulaczewski, Steffi; Dechent, Peter; Bönnemann, Carsten; Helms, Gunther; Kyllerman, Marten; Brück, Wolfgang; Frahm, Jens; Huehne, Kathrin; Gärtner, Jutta; Rautenstrauss, Bernd

    2008-07-01

    Mutations in the mitofusin 2 (MFN2) gene are a major cause of primary axonal Charcot- Marie-Tooth (CMT) neuropathy. This study aims at further characterization of cerebral white matter alterations observed in patients with MFN2 mutations. Molecular genetic, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) investigations were performed in four unrelated patients aged 7 to 38 years with early onset axonal CMT neuropathy. Three distinct and so far undescribed MFN2 mutations were detected. Two patients had secondary macrocephaly and mild diffuse predominantly periventricular white matter alterations on MRI. In addition, one boy had symmetrical T2-hyperintensities in both thalami. Two patients had optic atrophy, one of them with normal MRI. In three patients proton MRS revealed elevated concentrations of total N-acetyl compounds (neuronal marker), total creatine (found in all cells) and myo-inositol (astrocytic marker) in cerebral white and gray matter though with regional variation. These alterations were most pronounced in the two patients with abnormal MRI. DTI of these patients revealed mild reductions of fractional anisotropy and mild increase of mean diffusivity in white matter. The present findings indicate an enhanced cellular density in cerebral white matter of MFN2 neuropathy which is primarily due to a reactive gliosis without axonal damage and possibly accompanied by mild demyelination. PMID:18425620

  11. Markers of cerebral small vessel disease and severity of depression in the general population.

    PubMed

    Direk, Nese; Perez, Heidi Saavedra; Akoudad, Saloua; Verhaaren, Benjamin F J; Niessen, Wiro J; Hofman, Albert; Vernooij, Meike W; Ikram, M Arfan; Tiemeier, Henning

    2016-07-30

    The vascular depression hypothesis postulates that cerebral small vessel disease can cause or exacerbate depression in elderly persons. Numerous studies explored the association of imaging markers of cerebral small vessel disease including white matter lesions (WMLs) and lacunar infarcts with depressive symptoms or disorders. However, cerebral microbleeds have not been tested in depression. In the current study, we aimed to explore the association of WMLs, lacunar infarcts and cerebral microbleeds with depression continuum in a large population-based sample, the Rotterdam Study. Study population consisted of 3799 participants (aged 45 or over) free of dementia. WML volumes, lacunar infarcts and cerebral microbleeds were measured with brain magnetic resonance imaging. Depressive symptoms, depressive disorders and co-morbid anxiety disorders were assessed with validated questionnaires and clinical interview. WML volumes and lacunar infarcts were associated with depressive symptoms and disorders. Cerebral microbleeds, especially in deep or infratentorial brain regions, were related to depressive disorders only. Our results indicate that WMLs and lacunar infarcts might be non-specific vascular lesions seen in depressive symptoms and disorders. Association of cerebral microbleeds with more severe forms of depression may indicate impaired brain iron homeostasis or minor episodes of cerebrovascular extraversion, which may play a role in depression etiology. PMID:27254084

  12. Therapeutic interventions in cerebral palsy.

    PubMed

    Patel, Dilip R

    2005-11-01

    Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy. PMID:16391455

  13. Cerebral pathology post heart transplantation.

    PubMed

    Peteghem, S Van; Pauw, M De

    2015-04-01

    Cerebral pathology is frequently encountered post heart transplantation with a cumulative incidence of about 80% after 15 years. A broad spectrum of disease entities is reported, from minor abnormalities to life-threatening diseases. Although cerebral infections and malignancies are rare in this patient population, they have a high mortality rate. Since 1991, 171 orthotopic heart transplantations were performed at the Ghent University Hospital with a 10-year survival rate of 75%. Severe cerebral complications occurred in 10 patients, with epilepsy in 2 patients, cerebrovascular accidents in 4 patients, cerebral infections in 3 patients and a cerebral malignancy in 1 patient, resulting in a fatal outcome in 7 patients. We present four of these cases. PMID:25292206

  14. Accelerated Achievement

    ERIC Educational Resources Information Center

    Ford, William J.

    2010-01-01

    This article focuses on the accelerated associate degree program at Ivy Tech Community College (Indiana) in which low-income students will receive an associate degree in one year. The three-year pilot program is funded by a $2.3 million grant from the Lumina Foundation for Education in Indianapolis and a $270,000 grant from the Indiana Commission…

  15. ACCELERATION INTEGRATOR

    DOEpatents

    Pope, K.E.

    1958-01-01

    This patent relates to an improved acceleration integrator and more particularly to apparatus of this nature which is gyrostabilized. The device may be used to sense the attainment by an airborne vehicle of a predetermined velocitv or distance along a given vector path. In its broad aspects, the acceleration integrator utilizes a magnetized element rotatable driven by a synchronous motor and having a cylin drical flux gap and a restrained eddy- current drag cap deposed to move into the gap. The angular velocity imparted to the rotatable cap shaft is transmitted in a positive manner to the magnetized element through a servo feedback loop. The resultant angular velocity of tae cap is proportional to the acceleration of the housing in this manner and means may be used to measure the velocity and operate switches at a pre-set magnitude. To make the above-described dcvice sensitive to acceleration in only one direction the magnetized element forms the spinning inertia element of a free gyroscope, and the outer housing functions as a gimbal of a gyroscope.

  16. Plasma accelerator

    DOEpatents

    Wang, Zhehui; Barnes, Cris W.

    2002-01-01

    There has been invented an apparatus for acceleration of a plasma having coaxially positioned, constant diameter, cylindrical electrodes which are modified to converge (for a positive polarity inner electrode and a negatively charged outer electrode) at the plasma output end of the annulus between the electrodes to achieve improved particle flux per unit of power.

  17. Particle acceleration

    NASA Technical Reports Server (NTRS)

    Vlahos, L.; Machado, M. E.; Ramaty, R.; Murphy, R. J.; Alissandrakis, C.; Bai, T.; Batchelor, D.; Benz, A. O.; Chupp, E.; Ellison, D.

    1986-01-01

    Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV.

  18. [Noradrenaline and cerebral aging].

    PubMed

    Jouvet, M; Albarede, J L; Lubin, S; Meyrignac, C

    1991-01-01

    The central functions of norepinephrine (NE) are a recent discovery: regulation of alertness and of the wakefulness-sleep cycle, maintenance of attention, memory and learning, cerebral plasticity and neuro-protection. The anatomical, histological, biochemical and physiological properties of the central noradrenergic system: extreme capacity for ramification and arborization; slow conduction, non-myelinized axons with extrasynaptic varicosities producing and releasing NE; frequency of co-transmission phenomena, and; neuromodulation with fiber effect responsible for improvement in the signal over background noise ratio and selection of significant stimuli form a true interface between the outside world and the central nervous system, notably for the neocortex in the context of the cognitive treatment of information. This central noradrenergic system is involved in the neurophysiology and the clinical features of cerebral aging (ideation-motor and cognitive function slowing down, loss of behavioral adjustment), neuro-degenerative disorders (SDAT, Parkinson's disease), certain aspects of depression and less obvious conditions (head injuries, sequelae of cerebrovascular accidents, sub-cortical dementia). The recent development of medications improving alertness (adrafinil, modafinil) with a pure central action and specifically noradrenergic, may contribute to an improvement in these multifactorial disorders. PMID:1864252

  19. Cerebral cartography and connectomics

    PubMed Central

    Sporns, Olaf

    2015-01-01

    Cerebral cartography and connectomics pursue similar goals in attempting to create maps that can inform our understanding of the structural and functional organization of the cortex. Connectome maps explicitly aim at representing the brain as a complex network, a collection of nodes and their interconnecting edges. This article reflects on some of the challenges that currently arise in the intersection of cerebral cartography and connectomics. Principal challenges concern the temporal dynamics of functional brain connectivity, the definition of areal parcellations and their hierarchical organization into large-scale networks, the extension of whole-brain connectivity to cellular-scale networks, and the mapping of structure/function relations in empirical recordings and computational models. Successfully addressing these challenges will require extensions of methods and tools from network science to the mapping and analysis of human brain connectivity data. The emerging view that the brain is more than a collection of areas, but is fundamentally operating as a complex networked system, will continue to drive the creation of ever more detailed and multi-modal network maps as tools for on-going exploration and discovery in human connectomics. PMID:25823870

  20. Cerebral sinus venous thrombosis

    PubMed Central

    Alvis-Miranda, Hernando Raphael; Milena Castellar-Leones, Sandra; Alcala-Cerra, Gabriel; Rafael Moscote-Salazar, Luis

    2013-01-01

    Cerebral sinus venous thrombosis (CSVT) is a rare phenomenon that can be seen with some frequency in young patients. CSVT is a multifactorial condition with gender-related specific causes, with a wide clinical presentation, the leading causes differ between developed and developing countries, converting CSVT in a condition characterized by a highly variable clinical spectra, difficult diagnosis, variable etiologies and prognosis that requires fine medical skills and a high suspicious index. Patients who presents with CSVT should underwent to CT-scan venography (CVT) and to the proper inquiry of the generating cause. This disease can affect the cerebral venous drainage and related anatomical structure. The symptoms may appear in relation to increased intracranial pressure imitating a pseudotumorcerebri. Prognosis depends on the early detection. Correcting the cause, generally the complications can be prevented. Mortality trends have diminished, and with the new technologies, surely it will continue. This work aims to review current knowledge about CSVT including its pathogenesis, etiology, clinical manifestations, diagnosis, and treatment. PMID:24347950

  1. Cerebral sinus venous thrombosis.

    PubMed

    Alvis-Miranda, Hernando Raphael; Milena Castellar-Leones, Sandra; Alcala-Cerra, Gabriel; Rafael Moscote-Salazar, Luis

    2013-10-01

    Cerebral sinus venous thrombosis (CSVT) is a rare phenomenon that can be seen with some frequency in young patients. CSVT is a multifactorial condition with gender-related specific causes, with a wide clinical presentation, the leading causes differ between developed and developing countries, converting CSVT in a condition characterized by a highly variable clinical spectra, difficult diagnosis, variable etiologies and prognosis that requires fine medical skills and a high suspicious index. Patients who presents with CSVT should underwent to CT-scan venography (CVT) and to the proper inquiry of the generating cause. This disease can affect the cerebral venous drainage and related anatomical structure. The symptoms may appear in relation to increased intracranial pressure imitating a pseudotumorcerebri. Prognosis depends on the early detection. Correcting the cause, generally the complications can be prevented. Mortality trends have diminished, and with the new technologies, surely it will continue. This work aims to review current knowledge about CSVT including its pathogenesis, etiology, clinical manifestations, diagnosis, and treatment. PMID:24347950

  2. Cerebral blood flow velocity in two patients with neonatal cerebral infarction.

    PubMed

    Nishimaki, S; Seki, K; Yokota, S

    2001-04-01

    Cerebral blood flow velocity was measured in the middle cerebral artery of two patients who exhibited unilateral neonatal cerebral infarction during the neonatal period. Doppler studies demonstrated increases in cerebral blood flow velocity but decreases in the resistance index on the affected side of the middle cerebral artery in the neonate who developed hemiplegia with cystic encephalomalacia, although the neonate with normal neurologic outcome exhibited symmetric cerebral blood flow velocity and resistance index. The asymmetry in cerebral blood flow velocity measurements of both middle cerebral arteries may be useful to evaluate the severity of brain damage and predict the neurodevelopmental prognosis of unilateral neonatal cerebral infarction. PMID:11377112

  3. [Stereotactically targeted radiotherapy of cerebral arteriovenous malformations].

    PubMed

    Kimmig, B; Engenhart, R; Wowra, B; Höver, K H; Marin-Grez, M; Sturm, V

    1989-09-01

    A report is given about radiotherapy in 41 patients suffering from cerebral vessel anomalies. A modified linear accelerator was used in a moving field technique with multiple pendulum planes to apply single doses between 8 and 28 Gy by means of stereotaxis into the angiographically determined target volume. The medium follow-up is 23 months. The latency of radiogenic effects is between one and two years. Radiological controls with an interval of more than 18 months after therapy are available in 17 out of 41 patients. Angiographic investigation showed complete obliterations of pathological vessels in six out of these patients and partial obliterations in six patients; five patients remained unchanged. There were no acute complications. Seven patients presented neurological deficiencies with a latency of 6 to 12 months, however, in all cases but one they regressed completely. Even taking into consideration the small number of patients and the short time of observation, a comparison with the results of other radiotherapeutical proceedings allows to draw the conclusion that the presented technique of stereotaxic convergent-beam irradiation represents a relatively simple, reliable and, in case of precise indication, efficient method for the therapy of cerebral arteriovenous malformations. PMID:2678547

  4. Laser Speckle Imaging of Cerebral Blood Flow

    NASA Astrophysics Data System (ADS)

    Luo, Qingming; Jiang, Chao; Li, Pengcheng; Cheng, Haiying; Wang, Zhen; Wang, Zheng; Tuchin, Valery V.

    Monitoring the spatio-temporal characteristics of cerebral blood flow (CBF) is crucial for studying the normal and pathophysiologic conditions of brain metabolism. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution can be obtained. In this chapter, a laser speckle imaging (LSI) method for monitoring dynamic, high-resolution CBF is introduced. To improve the spatial resolution of current LSI, a modified LSI method is proposed. To accelerate the speed of data processing, three LSI data processing frameworks based on graphics processing unit (GPU), digital signal processor (DSP), and field-programmable gate array (FPGA) are also presented. Applications for detecting the changes in local CBF induced by sensory stimulation and thermal stimulation, the influence of a chemical agent on CBF, and the influence of acute hyperglycemia following cortical spreading depression on CBF are given.

  5. Compact accelerator

    DOEpatents

    Caporaso, George J.; Sampayan, Stephen E.; Kirbie, Hugh C.

    2007-02-06

    A compact linear accelerator having at least one strip-shaped Blumlein module which guides a propagating wavefront between first and second ends and controls the output pulse at the second end. Each Blumlein module has first, second, and third planar conductor strips, with a first dielectric strip between the first and second conductor strips, and a second dielectric strip between the second and third conductor strips. Additionally, the compact linear accelerator includes a high voltage power supply connected to charge the second conductor strip to a high potential, and a switch for switching the high potential in the second conductor strip to at least one of the first and third conductor strips so as to initiate a propagating reverse polarity wavefront(s) in the corresponding dielectric strip(s).

  6. BICEP's acceleration

    SciTech Connect

    Contaldi, Carlo R.

    2014-10-01

    The recent Bicep2 [1] detection of, what is claimed to be primordial B-modes, opens up the possibility of constraining not only the energy scale of inflation but also the detailed acceleration history that occurred during inflation. In turn this can be used to determine the shape of the inflaton potential V(φ) for the first time — if a single, scalar inflaton is assumed to be driving the acceleration. We carry out a Monte Carlo exploration of inflationary trajectories given the current data. Using this method we obtain a posterior distribution of possible acceleration profiles ε(N) as a function of e-fold N and derived posterior distributions of the primordial power spectrum P(k) and potential V(φ). We find that the Bicep2 result, in combination with Planck measurements of total intensity Cosmic Microwave Background (CMB) anisotropies, induces a significant feature in the scalar primordial spectrum at scales k∼ 10{sup -3} Mpc {sup -1}. This is in agreement with a previous detection of a suppression in the scalar power [2].

  7. White matter lesions and intra-arterial thrombolysis.

    PubMed

    Jung, Simon; Mono, Marie Luise; Findling, Oliver; Fischer, Urs; Galimanis, Aekaterini; Weck, Anja; De Marchis, Gian Marco; Ballinari, Pietro; Gralla, Jan; Brekenfeld, Caspar; Schroth, Gerhard; Arnold, Marcel; Mattle, Heinrich P; El-Koussy, Marwan

    2012-07-01

    The aim of the study was to assess the influence of white matter lesions in patients with acute ischemic stroke treated with intra-arterial thrombolysis (IAT). From September 2003 to January 2010, we treated 400 patients with IAT at our institution. Of these patients, 292 were evaluated with MRI scans and included in this observational study. Clinical data were collected prospectively. Outcome after 3 months was measured with the modified Rankin Scale (mRS); mRS 0-1 was considered as favorable outcome. White matter lesions were scored visually by two observers using the semiquantitative Scheltens and Fazekas scores. Logistic regression analysis was used to identify the association of white matter lesions and clinical outcome, recanalization, and cerebral hemorrhage. The severity of white matter lesions was inversely correlated with favorable outcome, survival and successful recanalization. White matter lesions were an independent predictor of outcome (OR 0.569, p = 0.007) and survival (OR 0.550, p = 0.018) and a weak but independent predictor for recanalization (OR 0.949, p = 0.038). Asymptomatic intracerebral bleeding after IAT was associated with white matter lesions in the basal ganglia in the univariate analysis (p = 0.036), but not after multivariable analysis. The severity of white matter lesions independently predicts clinical outcome and survival in patients treated with IAT. White matter lesions are also a weak but independent predictor for recanalization. Symptomatic intracranial bleeding after IAT are not associated with white matter lesions. Therefore, white matter lesions should not be considered as a contraindication against IAT. PMID:22249288

  8. Cerebral circulation, metabolism, and blood-brain barrier of rats in hypocapnic hypoxia

    SciTech Connect

    Beck, T.; Krieglstein, J.

    1987-03-01

    The effects of hypoxic hypoxia on physiological variables, cerebral circulation, cerebral metabolism, and blood-brain barrier were investigated in conscious, spontaneously breathing rats by exposing them to an atmosphere containing 7% O/sub 2/. Hypoxia affected a marked hypotension, hypocapnia and alkalosis. Cortical tissue high-energy phosphates and glucose content were not affected by hypoxia, glucose 6-phosphate lactate, and pyruvate levels were significantly increased. Blood-brain barrier permeability, regional brain glucose content and lumped constant were not changed by hypoxia. Local cerebral glucose utilization (LCGU) rose by 40-70% of control values in gray matter and by 80-90% in white matter. Under hypoxia, columns of increased and decreased LCGU and were detectable in cortical gray matter. Color-coded (/sup 14/C)2-deoxy-D-glucose autoradiograms of rat brain are shown. Local cerebral blood flow (LCBF) increased by 50-90% in gray matter and by up to 180% in white matter. Coupling between LCGU and LCBF in hypoxia remained unchanged. The data suggests a stimulation of glycolysis, increased glucose transport into the cell, and increased hexokinase activity. The physiological response of gray and white matter to hypoxia obviously differs. Uncoupling of the relation between LCGU and LCBF does not occur.

  9. Whiteness in Social Work Education Authentic White Allies

    ERIC Educational Resources Information Center

    Hornung, Rebecca

    2012-01-01

    This dissertation is guided by the following questions: How do People of Color define and experience White people as "authentic" allies? What does a White ally look like to People of Color? How do White allies view themselves as "authentic" White allies? What experiences lead White people to anti-racism and anti-racist praxis?…

  10. Cerebral venous angiomas

    SciTech Connect

    Olson, E.; Gilmor, R.L.; Richmond, B.

    1984-04-01

    Several unusual cases of cerebral venous angiomas as well as some characteristic cases are reported. The characteristic angiographic feature is that of a collection of dilated medullary veins draining into a single large draining vein, which appears first in the early venous phase and persists into the late venous phase of the arteriogram. Computed tomography (CT) was abnormal in 12/13 cases. The draining vein was the most common abnormality identified on CT. Coronal and sagittal reconstruction may be helpful in demonstrating the draining vein. A case of large twin venous angiomas, a case of hemorrhage from a venous angioma, and a case of a venous angioma with an incidentally associated glioblastoma are presented.