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PubMed2000

Incidence of focal white matter lesions in a population of hemophiliac children and their normal siblings. Hemophilia Growth and Development Study.

OBJECTIVE: This analysis was undertaken to evaluate the etiology and sequelae of 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of some participants enrolled in the Hemophilia Growth and Development Study (HGDS). MATERIALS AND METHODS: The HGDS is a multicenter study of the growth and development, neurological, neuropsychological, and immune functioning of a cohort of children and adolescents, 62% of whom were infected with HIV through the use of clotting factor concentrates, and their non-hemophiliac, non-HIV infected male siblings. The current investigation was conducted with all three groups of HGDS participants: HIV-positive hemophiliacs (n = 207), HIV-negative hemophiliacs (n = 126), and their siblings (n = 47). Magnetic resonance imaging was performed at each center, with a variety of 0.3 to 1.5 T instruments. Standard examinations included 5-mm-thick T1-weighted sagittal and axial images, intermediate, and T2-weighted axial images. A study of abnormalities of the coagulation system known to be associated with thrombotic events was conducted among a subgroup of participants (n = 51) from eight centers. RESULTS: Lesions were not associated with hemophilia-related factors, immune function, hematologic, or neurologic factors. There were no associations between the presence of white matter lesions and defects of coagulation in any of the assays completed. CONCLUSION: The 2- to 5-mm focal white matter hyperintensities on T2-weighted MR images of the brain were incidental findings in our study population.

Adolescent↗
PubMed2006

Regression of white matter hypodensities with age in Aicardi-Goutierés syndrome: a case report.

BACKGROUND: Aicardi-Goutierés syndrome (AGS) is a severe and progressive familial encephalopathy that is characterized by acquired microcephaly, intracranial calcification, white matter lesions, and chronic lymphocytosis with elevated levels of interferon-alpha in the cerebrospinal fluid. Although the degree of calcification and the severity of brain atrophy are variable, typically, the brain lesions appear to progress on successive examinations. CASE REPORT: We report a 7-year-old male patient who showed relative regression of white matter lesions with nonprogression of basal ganglia calcification and atrophy on follow-up magnetic resonance imaging and computed tomography scans. RESULTS: Magnetic resonance spectroscopy findings were normal. This, to our knowledge, is the first case report, which describes relative regression of the white matter changes in AGS.

Age Factors↗
PubMed2006

Corticobasal degeneration with focal, massive tau accumulation in the subcortical white matter astrocytes.

We report two sporadic cases of tauopathy with unusual neuropathological features. The ages of the patients at death were 86 and 74 years, and the disease durations were 4 and 3 years, respectively. The former patient showed progressive dementia and amyotrophy (autopsy revealed that severe cervical spondylosis was responsible for the amyotrophy), and the latter showed progressive parkinsonism and dementia. The essential brain pathologies were similar to each other; although ballooned neurons and astrocytic tau lesions (astrocytic plaques) were present in the affected cerebral cortex, the most striking finding was focal, much heavier accumulation of tau in the subcortical white matter. Moreover, double-labeling immunostaining, as well as Gallyas-Braak electron and AT8 immunoelectron microscopic studies strongly suggested that in the affected subcortical white matter, the accumulation of tau occurred mainly in the astrocytic processes. In the latter patient, for whom frozen brain tissue was available, immunoblotting of insoluble tau revealed a pattern compatible with that obtained from brain affected by typical corticobasal degeneration (CBD), and gene analysis of tau revealed no mutations, with a H1 haplotype. Finally, in both cases, the pathological diagnosis of CBD was considered to be appropriate. However, the tau pathology affecting the subcortical white matter astrocytes was very unusual for the disease.

Aged↗
PubMed2001

White matter preservation after spinal cord injury in ICAM-1/P-selectin-deficient mice.

We have previously demonstrated that mice deficient in ICAM-1 and P-selectin (ICAM-1/PS-/-) have improved functional recovery after spinal cord injury (SCI), compared to injured controls. In this study the spinal cords from wild-type and ICAM-1/PS-/- mice were evaluated histopathologically 14 days after severe compression-type SCI. Following injury there was an atrophy of the spinal cord. Significant sparing of total cross-sectional area was noted in ICAM-1/PS-/- mice compared to injured controls at the site of compression and in the distal peri-injury zone. Likewise, significant preservation of white matter area, as measured by Luxol staining, was found in mutant mice at the site of injury and in the proximal peri-injury zone. Gray matter damage was investigated by microtubule-associated protein 2 immunohistochemistry. Following severe SCI, a trend of gray matter sparing was noticed in ICAM-1/PS-/- animals. Quantitation of iba1 immunohistochemistry revealed that microglial reaction was significantly suppressed in the mutant animals. Astroglial reaction, visualized by GFAP immunostaining, did not differ between groups. Our results indicate that ICAM-1 and P-selectin are involved in autodestructive events provoked by the initial injury but the precise underlying mechanisms remain obscure.

Animals↗
PubMed2003

The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study.

BACKGROUND: In 10-15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability. METHODS: Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75% probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzke's expanded disability status scale (EDSS). RESULTS: Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearman's rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = -0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = -0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant. CONCLUSIONS: There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.

Adult↗
PubMed2006

Family-based association study of matrix metalloproteinase-3 and -9 haplotypes with susceptibility to ischemic white matter injury.

Susceptibility to ischemic damage to the subcortical white matter of the brain has a strong genetic basis. Dysregulation of matrix metalloproteinases (MMPs) contributes to loss of cerebrovascular integrity and white matter injury. We investigated whether sequence variation in the genes encoding MMP3 and MMP9 is associated with variation in leukoaraiosis volume, determined by magnetic resonance imaging, in non-Hispanic whites and African-Americans using family-based association tests. Seven hundred and fifty-six white and 671 African-American individuals from sibships ascertained through two or more siblings with hypertension were genotyped for 7 and 8 haplotype-tagging polymorphisms in the MMP3 and MMP9 genes, respectively. MMP3 sequence variation was significantly associated with variation in leukoaraiosis volume in Whites. Two common haplotypes with opposing relationships to leukoaraiosis volume were identified. MMP9 sequence variation was also significantly associated with variation in leukoaraiosis volume in both African-Americans and Whites. Different haplotypes contributed to these associations in the two racial groups. These findings add to the growing body of evidence from animal models and human clinical studies suggesting a role of MMPs in ischemic white matter injury. They provide the basis for further investigation of the role of these genes in susceptibility and/or progression to clinical disease.

Black or African American↗
PubMed2003

Relationship between structural modeling and hyperelastic material behavior: application to CNS white matter.

Recent measurements of the material properties of brain tissue allow an examination of the underlying microstructural basis in both physiological and pathophysiological conditions. The purpose of this study is to develop a mathematical relationship between microstructurally based models of the central nervous system (CNS) white matter and equivalent hyperelastic material models. For simplicity, time dependent material behavior is not included in this formulation. The microstructural representation is used to formulate structural property relationships for highly oriented white matter, and is mathematically compared to one isotropic and two anisotropic hyperelastic formulations. For the anisotropic characterizations, the population of axons in the white matter is assumed to align along one preferred direction of the material, yielding a transversely isotropic formulation. Relatively simple strain-energy functions incorporating material anisotropy provide sufficient flexibility to model the nonlinear behavior predicted from structurally based models, although the tangential stiffness of the hyperelastic approaches does not follow completely the behavior of the structurally based formulations. This analysis is an initial step towards linking microstructural aspects of the tissue to material models commonly used for large deformations, and may be an important step in relating predicted tissue deformation to the deformation and stress of cellular and subcellular structures.

Animals↗
PubMed2006

Sediment and suspended matter lead contamination in the gulf of Kavala, Greece.

Sediment and suspended particulate matter samples from 24 stations in the Gulf of Kavala have been examined for lead contamination. Grain size analysis and organic matter content were also performed. Total -- anthropogenic sediment lead concentrations and enrichment factors at stations close to harbors and chemical industries were found higher (up to 209-135 micro g/g and 4.12 respectively), in relation to concentrations from the rest of the coastal zone. In the above areas, increased suspended particulate lead in the bottom of the water column was also recorded (up to 109 micro g/g). Total sediment lead concentrations composed of high natural Pb background increased with decreasing grain size, suggesting their association with the fine fractions of the sediments (31.1-66.0% mud presence) and the organic matter content (6-9% higher values). Overall, higher total lead concentrations in the sediments, determined by this work, appear to be significantly different from those reported for the Gulf of Kavala in previous studies and similar to those detected in other highly contaminated eastern Mediterranean coastal areas.

Environmental Monitoring↗
PubMed2005

Evidence of nitrosative damage in the brain white matter of patients with multiple sclerosis.

Nitric oxide (NO) has been implicated in the pathophysiology of both experimental autoimmune encephalomyelitis and multiple sclerosis (MS). NO-mediated protein damage in MS appears to be confined to large plaques where 3-nitrotyrosine has been detected. To determine whether nitrosative damage takes place beyond visible MS plaques, the occurrence of various NO-triggered protein modifications in normal-appearing white matter (NAWM) of eight MS brains was assessed and compared to that in white matter (WM) of four control brains. As determined by amino acid analysis and western blotting, no evidence of tyrosine nitration was found in the MS samples studied, suggesting that they did not contain appreciable amounts of plaque-derived material. The amino acid composition of total myelin proteins and proteolipid protein (PLP) was also unaltered in the diseased tissue, as was the fatty acid composition of PLP. In addition, we detected no changes in the number of protein free thiols suggesting that oxidation do not occur to any appreciable extent. However, the levels of nitrite in MS-NAWM were higher than those in control WM, while in the MS-gray matter (GM) the concentration of this ion was unaltered. Furthermore, five of the MS samples analyzed, and the same as those with high levels of glial fibrilary acidic protein, showed increased amounts of protein nitrosothiols as determined by the "biotin switch" method. S-nitrosation of GM proteins was again normal. There was no indication of N-nitrosation of tryptophan and N-terminal amino groups in both control and MS tissue. Overall, the data suggests that WM, but not GM, from MS brains is subjected to considerable nitrosative stress. This is the first report to present direct evidence of increased protein S-nitrosation and nitrite content in the brain parenchyma of MS patients.

Adult↗
PubMed1977

Isolation of non-myelin plasma membranes unique to white matter.

A procedure is described for isolating two membrane fractions from rabbit spinal-cord white matter enriched with 5'-nucleotidase, a nonspecific plasma membrane marker, 2',3'-cyclic nucleotide phosphohydrolase, an oligodendroglial plasma membrane marker, and acetylcholinesterase, an axonal plasma membrane marker. While the two membrane fractions exhibited similar enrichments with respect to cyclic nucleotide phosphohydrolase, enrichments of 5'-nucleotidase and acetylcholinesterase were significantly greater in the heavier membrane fraction. Selected enzyme markers for cyto- and mitochondrial membranes were not detected. Moreover, gray matter did not yield homologous membrane fractions in the gradient when subjected to the identical procedure, indicating that the two membrane fractions were unique to white matter. While electronmicroscopic examination revealed that both membrane fractions were comtaminated with myelin, the heavier fraction was least contaminated and exhibited a fair degree of homogeneity with respect to single membrane vesicular profiles. It was concluded that both membrane fractions were enriched with oligodendroglial and axonal plasma membranes, with the heavier fraction containing significantly more axolemma.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1996

Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia.

This study examined whether the neuropsychological deficits observed in patients with schizophrenia were related to cortical gray matter volume deficits in these patients. All subjects were men and included 34 patients with DSM-III-R Schizophrenia and 47 age-matched healthy controls. Subjects received a battery of 21 tests, assessing four different functional domains: executive functions, short-term memory and production, declarative memory, and motor ability. MRI volumes were corrected for normal variation in head size and age, and neuropsychological test scores were corrected for normal variation in age. The schizophrenic group had significantly smaller cortical gray matter volumes (p < .05) and lower test scores in all functional domain than the control group (p = .0001). Within the schizophrenic group, lower scores in each domain were significantly correlated with smaller total cortical gray matter volumes; however, no predictable relationships were observed between neuropsychological test performance and the volumes of specific cortical regions.

Adult↗
PubMed1993

Age-related gliosis in the white matter of mice.

A histopathologic study of the brains from 96 mice, ranging in age from 3 to 57 months in age, documents an age-associated increase in hypertrophic astrocytes in white matter. This report of gliosis is distinct from previously reported proliferation of glial cells in the grey matter. Four genotypes, CBA/HT6J, C57BL/6J, B6CBAT6F1J, and B6C3F1 were positive for this age-related lesion. Most very old mice utilized in this study were calorically restricted, a dietary manipulation long known to result in increased longevity in rodents. Caloric restriction appears to delay the age associated increase of this lesion. Immunoperoxidase staining for the astrocyte-specific glial fibrillary acidic protein (GFAP) confirmed the progressive increase in the density of stainable astrocytes with increase in age. GFAP staining of white matter increased in both diet groups with age. These findings present an interesting model for the study of aberrant cellular activity and perhaps neurodegeneration, modulated by caloric restriction.

Aging↗
PubMed1993

Formation of reduced carbonaceous matter in basalts and xenoliths: reaction of C-O-H gases on olivine crack surfaces.

It has been suggested that the formation of reduced carbonaceous matter in basalts and mantle xenoliths occurs by heterogeneous reaction of volcanic gas on fresh, chemically active crack surfaces produced by thermal stresses during eruption and cooling. This hypothesis is supported by experiments at 400-800 degrees C on ¿010¿ surfaces of San Carlos olivine exposed to C-O-H gases generated by the decomposition of oxalic acid and oxalic acid dihydrate. Carbonaceous films form readily on these surfaces and achieve thicknesses comparable to those observed in natural samples (a few nanometers) in a matter of minutes. At relatively oxidizing conditions, the carbonaceous films consist principally of C-C and C-H bonded species with lesser amounts of C-O bonded species. At relatively reducing conditions, the carbonaceous films consist of subequal amounts of C-C/C-H, C-O, and metal-C species. Aliphatic and aromatic hydrocarbons and other thermally labile organic species are associated with carbonaceous films in some natural samples but none were detected in experimental samples from this study, leaving open the question of abiotic synthesis of organic matter on crack surfaces in basalts. Regardless, it is clear from the preliminary experiments reported here that crack surfaces in olivine (and probably other silicate minerals and glasses) are capable of stabilizing compounds that otherwise would not be stable in cooling lava.

Carbon↗
PubMed1994

A molecular and isotopic study of the organic matter from the Paris Basin, France.

Thirteen Liassic sedimentary rocks of increasing depth and three petroleums from the Paris Basin were studied for 13C/12C isotopic compositions and biological markers, including steranes, sterenes, methylphenanthrenes, methylanthracenes, and triaromatic steroids. The isotopic compositions of n-alkanes from mature sedimentary rocks and petroleums fall in a narrow range (2%), except for the deepest Hettangian rock and the Trias petroleum, for which the short-chain n-alkanes are enriched and depleted in 13C, respectively. Most of the molecular parameters increase over the 2000-2500 m depth range, reflecting the transformation of the organic matter at the onset of petroleum generation. In this zone, carbonate content and carbon isotopic composition of carbonates, as well as molecular parameters, are distinct for the Toarcian and Hettangian source rocks and suggest a migration of organic matter from these two formations. Two novel molecular parameters were defined for this task: one using methyltriaromatic steroids from organic extracts; the other using 1-methylphenanthrene and 2-methylanthracene from kerogen pyrolysates. The anomalous high maturity of the Dogger petroleum relative to the maturity-depth trend of the source rocks is used to estimate the minimal vertical distance of migration of the organic matter from the source rock to the reservoir.

Alkanes↗
PubMed1983

Familial Creutzfeldt-Jakob disease with extensive degeneration of white matter. Ultrastructure of peripheral nerve.

A case of Creutzfeldt-Jakob disease (CJD) in a 52-year-old man is described. At post mortem, extensive involvement of white matter was seen. A few similar cases have been reported mainly by Japanese authors. Our patients belonged to a French family in which 14 cases of CJD over three generations have been recorded. One of the patient's first cousins also had extensive white matter involvement. This is an unusual panencephalopathic form of CJD. The causes of the involvement of white matter are unknown. There was no clinical evidence of neuropathy but an electron-microscopic study of biopsied superficial peroneal nerve showed it to be present. Study of peripheral nerves is suggested for all patients with CJD.

Biopsy↗
PubMed1991

Fos RNA accumulation in multiple sclerosis white matter tissue.

In order to better characterize the molecular events that accompany lesion development in multiple sclerosis (MS), we studied the accumulation of RNA specific to the nuclear proto-oncogenes c-fos and c-myb in post mortem white matter brain tissue. RNA was prepared from plaque and periplaque regions of 6 different MS brains, from "normal" white matter regions of 3 MS brains and from 6 normal control samples. Quantitation of specific RNA corresponding to each proto-oncogene was performed by Northern blot hybridization and by scanning densitometry. Results indicate a 2-fold increase in c-fos RNA in MS white matter, compared to control tissue. No c-myb signal was identified in any sample. In situ hybridization studies confirmed the selective upregulation of c-fos RNA levels in MS tissue, and suggested that glial cells and not inflammatory cells were responsible for the enhanced c-fos signal. These results suggest that persistent glial cell activation is present within chronic MS lesions irrespective of whether the lesions are active (e.g., inflammatory) or inactive.

Blotting, Northern↗
PubMed1992

White matter lesions in the elderly.

The advent of neuroimaging has brought medical attention to the frequency of unsuspected white matter lesions in the brains of elderly people. In 1987 Hachinski suggested the term "leuko-araiosis" to identify such white matter abnormalities detected by computed tomography and magnetic resonance imaging to emphasize that their etiology and clinical relevance require clarification. Since then, leuko-araiosis has been recognized among approximately ten percent of apparently normal, elderly people over age sixty-five. The severity and frequency of leuko-araiosis increases with advancing age, risk factors for stroke, history of strokes particularly of the lacunar type and dementia of both the vascular and Alzheimer type. Current concepts concerning the pathogenesis and neurological concomitants of leuko-araiosis are reviewed. The etiology of leuko-araiosis may be heterogeneous but is most likely ischemic in nature. However, as white matter lesions progress among the elderly they are likely to become associated with cognitive impairments and motor dyspraxias presumably resulting from cortico-subcortical disconnections, particularly involving the frontal cortex and basal ganglia and may themselves be considered a radiological "risk factor" or precursor for dementia.

Aged↗
PubMed1995

White matter abnormalities in congenital muscular dystrophy.

Central nervous system (CNS) characteristics were examined in seventeen patients with autosomal recessive classic or "pure" congenital muscular dystrophy (CMD). In three patients, neuroradiological examination (CT/MRI) indicated hypodense white matter areas. Two out of these three patients had epilepsy (seizures and epileptic discharges on their EEG). Only two of the remaining patients had epileptic EEG discharges, but without clinical seizures. By comparing our results to data in the literature, we could conclude that the classic or "pure" form of CMD can be subdivided into two subtypes, i.e. those with and those without white matter hypodensities. A mild form of epilepsy or an epileptic predisposition on EEG can be part of the subtype with white matter hypodensities.

Adolescent↗