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[A case of herpes simplex encephalitis with cerebral white matter lesion after acyclovir administration].

Herpes simplex virus (HSV) is regarded as an agent that selectively affects temporal and frontal lobes with necrosis and hemorrhage, and no case of herpes simplex encephalitis (HSE) with white matter lesion in a diffuse fashion has previously been reported. A 2-year-old boy developed high fever, right hemi-convulsions and lethargy. Computed tomography (CT) showed wedge-shaped areas of high density in the left frontal region, whereas, cerebral angiography disclosed no vascular abnormality. T1-weighted magnetic resonance imaging (MRI) demonstrated cortical changes which were similar to those illustrated by CT. However, T2-weighted images depicted further spread high intensities of the lesion. The patient's symptoms spontaneously disappeared before an antiviral drug, acyclovir, was administered. After the significant increase of HSV antibody titers in serum and cerebro-spinal fluid (CSF) established a definite diagnosis, acyclovir was intravenously given at a daily dosage of 30 mg/kg for a period of 6 days in order to prevent the recurrence of HSE. Two months later, T2-weighted MRI visualized a diffuse lesion of increased signal intensities involving the white matter of both hemispheres, while both CSF protein and myelin basic protein were significantly elevated. Despite of these changes of the white matter, our patient developed a few symptoms such as mild speech disturbance, slight weakness of the right upper limb and sialorrhea. Although the mechanism of these changes in the white matter remains obscure, it is postulated that a direct invasion of HSV to the white matter, an immunological disorder following HSV infection and a side effect of acyclovir could have triggered a reversible process of demyelination of the cerebral white matter.

Acyclovir↗

Rumen dry matter degradability and apparent digestibility of variously treated rice hulls.

Rice hulls from Hungary, Colombia, and Cambodia were used for measuring with the nylon bag method the dry matter degradability in the rumen of sheep. After 48 h rumen incubation time the dry matter loss varied between 10.0 and 27.7%. The 48 h rumen dry matter loss of rice hulls from Hungary increased from 14.0 (untreated control) only to 17.9, 20.1, and 17.0% after chemical treatment with 2% NaOH, 4% CaO, and 4% urea, respectively. gamma-irradiation with doses of 0, 0.1, 0.25, 0.5, 1, and 2 MGy effected rumen dry matter losses of unground rice hulls from Hungary of 6.4, 14.5, 13.5, 21.3, 37.1, and 70.5%. The apparent digestibility of organic matter of untreated rice hulls from Hungary amounted to 19.2%, as found in tests with wethers. The main reasons of low digestibility and the negligible effect of chemical treatments are the high contents of lignin (ca. 15%) and silica (up to 23% of the dry matter). Therefore rice hulls are not suitable as feedstuff for ruminants.

Animal Feed↗

Astrocytes in Alzheimer's disease gray matter express alpha 1-antichymotrypsin mRNA.

The serine protease inhibitor alpha 1-antichymotrypsin (ACT) has been shown to be tightly associated with the amyloid found in plaque cores and blood vessels in the brains of patients with Alzheimer's disease (AD). Although the ACT found in plaques could be derived from the high levels of ACT in serum, previous Northern analysis revealed that ACT mRNA is produced locally in AD gray matter at much higher levels than in control gray matter. To determine which brain cells express ACT mRNA, we conducted in situ hybridization with 35S-labeled cRNA probes on hippocampal sections from four AD and three control cases. To identify astrocytes unequivocally, some of the hybridized sections were immunostained for glial fibrillary acidic protein, which is astrocyte-specific. Our results showed numerous astrocytes that were intensely labeled by the probe for ACT mRNA throughout the subicular gray matter of the AD cases. In contrast, astrocytes in control gray matter were rarely labeled by the probe for ACT mRNA. Examination of plaque cores in the AD subiculum showed that some astrocytes intensely labeled by the probe for ACT mRNA were closely associated with virtually every plaque core. Our results also showed many astrocytes in both AD and control white matter that were intensely labeled by the probe for ACT mRNA, and a small fraction of the astrocytes in a juvenile cerebellar astrocytoma that we examined were found to produce high levels of ACT mRNA. In every area in which astrocytes expressing ACT mRNA were found, astrocytes producing no detectable ACT message were also present. Our findings indicate that astrocytes produce the increased ACT mRNA in AD gray matter observed by Northern analysis, but they also show that ACT mRNA expression by astrocytes is not unique to AD. The presence of astrocytes expressing ACT mRNA near, and extending processes towards, plaque cores strongly suggests that some if not all of the ACT associated with amyloid plaque cores is produced by astrocytes surrounding the cores.

Alzheimer Disease↗

Vascular resistance, metabolism and EEG within cerebral grey and white matter during hypoxia in neonatal piglets.

To study unsolved problems of the causal chain of neonatal hypoxic brain damage in 31 hypoxic newborn non-anesthetized piglets cerebro-vascular, metabolic and EEG reactions were investigated (FiO2: 0.06-0.10, 1 h). Only in artificially ventilated newborn piglets this acute hypoxic hypoxia provoked a vital decompensation by critical depression of mean arterial blood pressure (less than or equal to 4.67 kPa [35 mmHg]) and/or a critical increase of vascular resistance (Rc) in the cerebral white matter (greater than 50%). Spontaneously breathing piglets survived always showing hyperventilation, higher pHa and an increase of cerebral O2-consumption in cerebral grey matter, partly also in white matter. This critical increase of Rc was related to a critical decrease of O2-consumption in the white matter and an insufficient decrease of Rc of the grey matter. The observed strong metabolic and hemodynamic differences between these two brain compartments can explain the evaluated special morphological vulnerability of cerebral white matter in ventilated animals.

Animals↗

Distribution of anticonvulsant drugs in gray and white matter of human brain.

Gray and white matter were obtained during neurosurgical therapy of focal epilepsy from 17 patients. In 10 patients, receiving only phenobarbital, the drug was uniformly distributed between gray and white matter. Phenytoin concentrations averaged 1.4-fold greater in white matter than in gray matter when expressed per gram wet weight of tissue. The gray matter/plasma ratio of phenytoin was approximately 2-fold greater than that of phenobarbital. Carbamazepine levels were also slightly greater in white matter. The data revealed wide differences between drugs in the relative concentrations in gray and white matter, which must be taken into account in any quantitative studies of anticonvulsant drug levels in the brain.

Anticonvulsants↗

White matter MR hyperintensities in adult patients with congenital rubella.

PURPOSE: To observe and quantify white matter hyperintensities on MR images in adults with schizophrenialike symptoms who had had congenital rubella, in order to elucidate the neuropathologic sequelae of this perinatal viral infection and to explore the potential relationship of these lesions to schizophrenia. METHODS: Eleven deaf adult patients with documented prenatal rubella virus infection and schizophrenialike symptoms were compared with 19 age-matched patients with early-onset schizophrenia who did not have congenital rubella and with 18 age-matched control subjects. All MR images (obtained at 1.5 T) were evaluated by a neuroradiologist who was blinded to diagnosis and were rated for white matter lesions on a five-point scale: 0 = no lesions; 1 = 1 lesion less than 1 mm in diameter; 2 = 1 to 4 lesions 1 mm or greater; 3 = 5 to 10 lesions; 4 = more than 10 lesions or a single lesion more than 1 cm in diameter. In addition, the white matter hyperintensities were volumed objectively with a manual threshold technique. RESULTS: Ratings of white matter lesions were significantly higher in the rubella patients than in the control subjects: 6 of the 11 patients had ratings greater than 1 compared with 1 of the 18 control subjects and none of the 19 schizophrenic patients. Also, MR images in five rubella patients received ratings at the highest end of the scale of abnormality (3 or 4). The white matter hyperintensities were characterized as bilateral T2 signal hyperintensities in periventricular and subcortical regions, punctate or linear in shape; they were observed predominantly in parietal lobes. CONCLUSION: This quantitative MR study of adult rubella patients disclosed abnormal white matter lesions that may correspond to neurovascular lesions known neuropathologically. They do not appear to be directly related to schizophrenialike symptoms.

Adult↗

[Diffusional anisotropy in the cerebral white matter in Alzheimer-type dementia].

To investigate changes in water diffusion in the cerebral white matter in Alzheimer-type dementia (AD), diffusion MRI studies were performed on 11 patients with AD without hyperintensity lesions on T2-weighted images, and 10 age-matched controls. In the anterior and posterior white matter around the lateral ventricule, and the splenium of the corpus callosum, the apparent diffusion coefficients (ADCs), in which the diffusion gradient was applied perpendicular to the predominant fiber direction, were significantly higher in patients with AD than in the controls. However, those in which the diffusion gradient was applied parallel to the predominant fiber direction, there were no significant difference in ADCs between patients and controls. Therefore, diffusional anisotropy was lost in the white matter. These results suggest that demyelination occurs in patients with AD even in apparently normal white matter (without signal abnormalitis). Degeneration related to grey matter encephalopathy may be a possible explanation of the demyelinating process in the white matter.

Alzheimer Disease↗

Dye coupling between spinal cord oligodendrocytes: differences in coupling efficiency between gray and white matter.

Oligodendrocytes express two gap junction proteins, connexin32 (Cx32) and Cx45. To test for functional coupling between oligodendrocytes, cells were filled with the (Cx32-permeable) dyes Lucifer Yellow (LY) and Neurobiotin. Cells in slices from rat spinal cord were dialyzed via the patch pipette containing the dye while recording with the patch-clamp technique. The dye-labeled cells were identified as oligodendrocytes by their characteristic pattern of membrane currents and by morphology. In gray matter, 18% of the injected cells (N = 94) were coupled to more than three adjacent cells (slices from postnatal day 1 to 19). In contrast, in white matter, the dye was restricted to the injected cell (N = 63 for Lucifer Yellow injection only; N = 11 for LY and Neurobiotin) indicating a lack of functional coupling. Immunolabeling of Cx32 in mature oligodendrocytes of white matter revealed that the gap junction protein is localized on the cell bodies and abaxonal processes which occupy non-overlapping territories. In immature white matter and gray matter, Cx32 is mostly concentrated in the somatic region of the cells. In addition to Cx32, we have obtained immunocytochemical data that oligodendrocytes can express Cx45 with a labeling pattern different from the Cx32 expression. Two alternative interpretations of the coupling data are discussed: 1) that the presence of Cx32 in mature white matter oligodendrocytes does not serve for communication between cells, but rather for communication within oligodendrocytes in the sense of autocellular coupling, or 2) that the glial syncytium is furnished with a high degree of functional rectification at the oligodendrocytic side.

Animals↗

Causal relationship between white matter structural connectivity and epilepsy.

White matter structural connectivity has recently been linked to epilepsy pathogenesis, yet its causal role remains unclear. This study used Mendelian randomization (MR) to investigate the causal relationship between white matter structural connectivity and epilepsy. GWAS summary statistics for white matter structural connectivity were sourced from the UK Biobank, while epilepsy data were obtained from FinnGen R10 and the International League Against Epilepsy (ILAE). Our MR analysis revealed significant causal links between white matter structural connectivity and epilepsy risk. Increased connectivity between the right hemisphere visual and salience/ventral attention networks (RH Vis to RH Sal/VentAttn WMSC) was associated with higher epilepsy risk in FinnGen_R10_FE_STRICT (OR&#xa0;=&#xa0;2.25, 95&#xa0;% CI&#xa0;=&#xa0;1.43-3.56, p&#xa0;<&#xa0;0.01, FDR P&#xa0;=&#xa0;0.019). Conversely, increased connectivity between left and right hemisphere salience/ventral attention networks (LH Sal/VentAttn to RH Sal/VentAttn WMSC) was linked to reduced epilepsy risk in FinnGen_R10_GE_STRICT (OR&#xa0;=&#xa0;0.17, 95&#xa0;% CI&#xa0;=&#xa0;0.07-0.46, p&#xa0;<&#xa0;0.01, FDR P&#xa0;=&#xa0;0.033). A total of 15 nominally significant associations were identified across datasets. These findings suggest a causal relationship between white matter structural connectivity and epilepsy, offering insights into disease mechanisms and potential therapeutic targets.

Humans↗

The cellular associates of late life changes in white matter microstructure.

The microstructural architecture of white matter supporting information flow across local circuits and large-scale networks changes throughout the lifespan. However, the genetic and cellular factors underlying age-related variations in white matter microstructure have yet to be established. Here, we examined the genetic associates of individual differences in diffusion-based measures of white matter in a population-based cohort (N=29,862) from the UK Biobank. Estimates of heritability from Genome-Wide Association Study (GWAS) data revealed that genetic factors are linked to population variability in 96.1% of 432 tract microstructural measures. The presence of shared genetic influences was observed to be greater within, relative to between, broad tract classes (commissural, association, projection, and complex cerebellar). Age associations with microstructural changes were estimated across diffusivity measures, with association class tracts showing the greatest vulnerability to age-related decline in older adults. Analyses of imputed cellular associates of age-related changes in white matter revealed a preferential relationship with cell gene markers of oligodendrocytes and other glial cell types, with sparse relationships observed for inhibitory and excitatory cells. These data indicate that white matter tract microstructure is shaped by genetic factors and suggest a role for glial cell-related transcripts in late-life changes in the structural wiring properties of the human brain.

Aging↗

Chemical composition of organic matter in extremely acid, lignite-containing lake sediments impacted by fly ash contamination.

In the Lusatian lignite mining district of eastern Germany, extremely acid lakes developed during ground water rising after exploitation of lignite in open-cast mines. The reasons of plant colonization (Juncus bulbosus L.) of some lakes exhibiting moderate pH values while others remain extremely acid and unvegetated are unknown. Alkalinity gain may be achieved by addition of alkaline materials and/or decomposition of organic matter. Our objective was to examine fly ash deposition and the resulting changes in organic matter composition in the uppermost 0 to 5 cm of the sediment sampled from vegetated and unvegetated lakes. Bulk soil and particle size fractions were analyzed for elemental composition, magnetic susceptibility, and chemical structure of the organic matter by 13C solid-state nuclear magnetic resonance (NMR) spectroscopy. The lignite content of the samples was estimated by 14C activity measurements. The pH values decreased with increasing depth and the changes in pH were found to be correlated with changes in magnetic susceptibility. Carbon and nitrogen contents were found to decrease with increasing depth. The C to N ratios are consistent with the (i) the presence of decomposing plant residues and/or microbial material such as algae in the upper 0 to 5 cm of the sediment and (ii) the dominance of lignite in the layers below this depth as confirmed by 14C activity measurements. The structural analyses of the particle size separates from the 0- to 5-cm depth were consistent with the presence of organic matter derived from plant material. This study confirms that fly ash is an important source of alkalinity in the upper 0 to 5 cm of the sediment that enhanced plant growth and led to enrichment of the sediment with organic matter derived from plant material.

Carbon↗

Periventricular and white matter magnetic resonance imaging hyperintensities do not differ between Alzheimer's disease and normal aging.

We studied normotensive and nondiabetic subjects, free of cardiac disorders, to determine whether Alzheimer's disease is a possible factor of magnetic resonance imaging (MRI) white matter or periventricular hyperintensities, and to investigate relationships between computed tomographic scan and MRI changes. We failed to reveal (1) any difference in the severity of MRI white matter and periventricular hyperintensities between patients and controls, (2) any correlation of MRI white matter and periventricular hyperintensities with either ages or Mini-Mental State Examination scores. We found (1) a poor interobserver agreement, and (2) a correlation between computed tomographic scan and MRI white matter changes but not between computed tomographic and MRI periventricular changes. We conclude that MRI periventricular and white matter hyperintensities are frequent incidental findings in the elderly and do not significantly differ between patients with Alzheimer's disease and healthy controls.

Aged↗

Comparison of postmortem magnetic resonance imaging and neuropathologic findings in the cerebral white matter.

Two types of high-signal intensity abnormalities are frequently found bilaterally in the cerebral white matter of brains of elderly patients on T2-weighted magnetic resonance imaging (MRI) scans. One is located in the immediate periventricular region; the other, in the deep subcortical white matter (centrum semiovale). The diagnostic implications of this second type continue to be uncertain. To determine the neuropathologic correlates of these lesions, the brains from seven elderly patients were fixed in buffered formaldehyde solution, subjected to MRI scanning, and examined neuropathologically. Variable degrees of bilateral periventricular (subependymal) sharply defined areas of high-signal intensity were found in all the brains, and the larger of these showed corresponding areas of myelin pallor with gliosis and dilated perivascular spaces. Discrete bilateral patches of high-signal intensity were found in the centrum semiovale in five patients. Myelin and axon stains showed varying degrees of diffuse white matter pallor in many areas examined, both with and without these areas of high-signal intensity on MRI scans. Neither the myelin nor the axon stains showed discrete white matter abnormalities that corresponded to the MRI findings. We believe that these changes, so commonly found on MRI scans in the elderly, reflect actual changes in the white matter but that their nature and clinical significance need to be elucidated.

Aged↗

Apolipoprotein E epsilon4 allele, temporal lobe atrophy, and white matter lesions in late-life dementias.

OBJECTIVE: To examine the relationship between the apolipoprotein E (APOE) epsilon4 genotype, medial temporal lobe atrophy, and white matter hyperintensities on magnetic resonance imaging in late-life dementias. DESIGN: Structural magnetic resonance imaging study using T2-weighted and proton density-weighted axial scans and T1-weighted coronal scans. SETTING: Community-dwelling population of elderly patients prospectively chosen from a clinical case register of consecutive referrals to old age psychiatry services. SUBJECTS: Twenty-five subjects with Alzheimer disease (by criteria of the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; mean age, 77.8 years), 22 subjects with dementia with Lewy bodies (consensus criteria; mean age, 77.2 years), and 24 subjects with vascular dementia (by criteria of the National Institute of Neurological Disorders and Stroke and the Association International pour la Recherche et l'Enseignement en Neurosciences; mean age, 76.9 years) were selected. Subjects were well matched for age, sex, duration of illness, and cognitive function. MAIN OUTCOME MEASURES: The APOE genotype was determined using the polymerase chain reaction method, and medial temporal lobe atrophy and white matter hyperintensities (periventricular and deep white matter) were visually rated using standardized scales. RESULTS: In all subjects with dementia, no significant associations were noted between APOE epsilon4 status and medial temporal lobe atrophy (mean score: 0 epsilon4 = 4.5, 1 epsilon4 = 4.5, and 2 epsilon4 = 4.3; P = .90), periventricular hyperintensities (0 epsilon4 = 3.3, 1 epsilon4 = 3.1, and 2 epsilon4 = 2.9; P = .83), and white matter hyperintensities (0 epsilon4 = 5.3, 1 epsilon4 = 4.9, and 2 epsilon4 = 4.9; P = .79). CONCLUSIONS: The APOE epsilon4 allele does not determine medial temporal lobe atrophy or white matter lesions, as measured by magnetic resonance imaging in patients with Alzheimer disease, vascular dementia, or dementia with Lewy bodies. Although APOE epsilon4 may modify the risk for acquiring dementia, this finding provides further evidence that APOE epsilon4 does not influence pathological processes thereafter.

Age Factors↗

Brain white matter impairment in congenital adrenal hyperplasia.

BACKGROUND: Congenital adrenal hyperplasia (CAH) is an inherited recessive disorder of adrenal steroidogenesis. Past reports suggested that brain white matter could be involved in CAH. OBJECTIVE: To detect the presence, and possible changes over time, of brain white matter abnormalities in patients with CAH. DESIGN: Neurological examination and brain magnetic resonance imaging (MRI) that were repeated in 12 patients after a mean interval of 11 years. SETTING: Pavia, northern Italy. Patients Twenty-two patients with CAH. MAIN OUTCOME MEASURES: Evaluation of clinical neurological findings and brain MRI T2-weighted images. RESULTS: Ten (45%) of 22 patients with CAH had white matter abnormalities (diffuse in 4 cases, focal in 3 cases, and both diffuse and focal in 3 cases) on MRI. The MRI findings never changed over repeated assessments. CONCLUSIONS: Subclinical brain white matter involvement is frequent in CAH. This might be due to hormonal imbalance during brain development or corticosteroid treatments. Our study findings indicate that a relationship with demyelinating diseases can also be suggested. Diagnosis of CAH should be suspected in young subjects with brain MRI white matter abnormalities that are not otherwise explicable.

Adolescent↗

Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study.

BACKGROUND: The Heschl gyrus and planum temporale have crucial roles in auditory perception and language processing. Our previous investigation using magnetic resonance imaging (MRI) indicated smaller gray matter volumes bilaterally in the Heschl gyrus and in left planum temporale in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis. We sought to determine whether there are progressive decreases in anatomically defined MRI gray matter volumes of the Heschl gyrus and planum temporale in patients with first-episode schizophrenia and also in patients with first-episode affective psychosis. METHODS: At a private psychiatric hospital, we conducted a prospective high spatial resolution MRI study that included initial scans of 28 patients at their first hospitalization (13 with schizophrenia and 15 with affective psychosis, 13 of whom had a manic psychosis) and 22 healthy control subjects. Follow-up scans occurred, on average, 1.5 years after the initial scan. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left Heschl gyrus (6.9%) and left planum temporale (7.2%) compared with patients with first-episode affective psychosis or control subjects. CONCLUSIONS: These findings demonstrate a left-biased progressive volume reduction in the Heschl gyrus and planum temporale gray matter in patients with first-episode schizophrenia in contrast to patients with first-episode affective psychosis and control subjects. Schizophrenia but not affective psychosis seems to be characterized by a postonset progression of neocortical gray matter volume loss in the left superior temporal gyrus and thus may not be developmentally fixed.

Adolescent↗

Brain white matter anatomy of tumor patients evaluated with diffusion tensor imaging.

We applied multislice, whole-brain diffusion tensor imaging (DTI) to two patients with anaplastic astrocytoma. Data were analyzed using DTI-based, color-coded images and a 3-D tract reconstruction technique for the study of altered white matter anatomy. Each tumor was near two major white matter tracts, namely, the superior longitudinal fasciculus and the corona radiata. Those tracts were identified using the color-coded maps, and spatial relationships with the tumors were characterized. In one patient the tumor displaced adjacent white matter tracts, whereas in the other it infiltrated the superior longitudinal fasciclus without displacement of white matter. DTI provides new information regarding the detailed relationship between tumor growth and nearby white matter tracts, which may be useful for preoperative planning.

Adult↗

Exploring white matter tracts in band heterotopia using diffusion tractography.

Band heterotopia is a malformation of cortical development characterized by bands of gray matter in the white matter parallel to the surface of the neocortex. Histopathological studies have suggested that small white matter tracts pass through the heterotopia, and functional magnetic resonance imaging studies have shown activation in the malformation. We used diffusion tractography to explore the anatomical connectivity of band heterotopia and, in particular, whether in vivo white matter tracts traverse the heterotopic gray matter. Five patients with band heterotopia and five control subjects were scanned with whole brain diffusion tensor imaging. Anisotropy maps were calculated. Using fast marching tractography, we produced maps of connectivity and tract traces from two seed points, in the splenium of the corpus callosum and the right parietal lobe. Eigenvectors were found to pass through the band heterotopia in an aligned fashion. Patterns for maps of connectivity were similar in patients and control subjects. Areas of high connectivity were found in the band heterotopia and in cortical areas on the far side of the malformation from the seed point. The tracts hence appeared to traverse or end within the band heterotopia. The results are in agreement with previous histopathological studies and indicate the structural basis of the functional connectivity and absence of focal deficits in these patients.

Adult↗