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A comparison of the regeneration potential of dorsal root fibers into gray or white matter of the adult rat spinal cord.

To assess the role of white matter inhibition as a barrier to neurite outgrowth in vivo, we unilaterally transected three consecutive lumbar dorsal roots (L4-L6), incised the spinal cord, and transplanted the peripheral stump of L4 either medially onto the white matter of the dorsal columns or laterally, just superficial to the gray matter of the dorsal horn at the level of L5. Three weeks to seven months later, the translocated root was retransected, and its central stump was anterogradely labeled with HRP. The staining pattern demonstrated that regenerating sensory axons had entered the spinal cord from both medially and laterally placed roots. Axonal staining from medially placed dorsal roots (onto the white matter of the dorsal columns) was sparse and limited to the white matter. Staining of laterally placed roots revealed a small subpopulation of regenerating axons which had entered the gray matter and formed terminal arbors. Successful axonal regeneration into the gray matter, albeit minimal, was associated with a localized and limited inflammatory response near the sites of axonal ingrowth.

Animals↗

White matter necrosis in very low birth weight infants: neuropathologic and ultrasonographic findings in infants surviving six days or longer.

We describe the neuropathologic and ultrasonographic findings in 22 very low birth weight infants (mean weight 948 gm) who survived at least 6 days and for whom cranial ultrasonography had been performed three or more times in life. White matter necrosis was found in 15 of the 22 subjects and was judged chronic (5 days' duration or longer) in seven subjects. The most common pattern was diffuse necrosis of hemispheric white matter, found in 10 of 15 infants; restriction of necrosis to the periventricular region was found in only three infants. The classic histologic features of periventricular leukomalacia were absent from 7 of the 15 infants with necrosis. Seventeen infants had intraventricular hemorrhage, but extension of ventricular blood into white matter unaffected by infarction was not found. Two ultrasonographic features were associated with white matter necrosis: increased parenchymal echogenicity and ventricular enlargement. One or both of these findings were present in 67% of infants with white matter necrosis, in 90% of infants with diffuse necrosis, but in no infant without necrosis. Increased parenchymal echogenicity was seen in all four infants with hemorrhagic necrosis, in 60% of infants with diffuse necrosis, but in none of the five infants with localized necrosis. We conclude that the very small infants now dying in nurseries have a form of white matter damage that is more extensive than, and in some cases histologically different from, periventricular leukomalacia as originally described. Ultrasonography as used in this study identified most but not all infants with pathologically verified white matter necrosis.

Brain↗

Fouling characteristics of NF and RO operated for removal of dissolved matter from groundwater.

A pilot study had been performed for about 6 months in order to investigate the removal efficiency of dissolved matter and its fouling potential during nanofiltration (NF) and reverse osmosis (RO) of local groundwater that was pretreated with an ultrafiltration (UF) membrane system. After pilot plant operation, autopsy tests were performed to identify the characteristics of foulants that were attached to the membrane surface. In the autopsy tests, the flux recovery for each specific cleaning scheme (hydraulic washing, acid cleaning, and alkaline cleaning) was also measured using a dead-end filtration cell unit. The washing solution used in each chemical cleaning was analyzed to identify major components of the foulants, and the membrane surface was observed using the scanning electron microscopy (SEM). Among three kinds of membranes tested, one NF and two RO membranes, the NF and RO1 membranes showed a rapid flux decline after 100 days of operation. Especially, the RO1 membrane showed the more serious flux decline than the NF membrane. The RO2 membrane, with the lowest recovery rate, demonstrated a gradual flux decline. The removal efficiency of dissolved inorganic matter (as conductivity) for each NF, RO1 and RO2 membrane was 76.3%, 88.2% and 95.3%, respectively. The removal of dissolved organic matter (as total organic carbon) was found to be about 80% for both NF and RO membranes used in this study. During the membrane autopsy tests, five sections of the fouled membrane were cut along each NF and RO membrane module from the feed inlet side to the concentrate outlet side, the specific flux for each membrane section was measured before and after each cleaning step. As expected, the degree of fouling was intensified along the membrane surface as the feed flow approached the outlet. Based on the analysis results of wash water used in each cleaning step, the major foulants attached to the membrane surface appeared to be Ca bound with inorganic matter and Si bound with organic matter. Fe seemed to be a great contributor to irreversible fouling. The SEM analysis indicated that the organic matter was forming the first fouling layer close to the membrane and that the inorganic matter was layered top of the organic fouling layer in a tetragonal shape. Any evidence of biofouling was not observed in this study because most of microorganisms had been already removed by the UF pretreatment.

Equipment Failure↗

Quantification of the dissolved organic matter effect on the sorption of hydrophobic organic pollutant: application of an overall mechanistic sorption model

This study presents an overall sorption model to estimate the sorption equilibrium coefficients of hydrophobic organic pollutants for heterogeneous aquatic systems. This proposed model combines a series of sorption equilibrium relationships including the adsorption of dissolved organic matters on particulates, the binding between organic pollutants and dissolved organic matters, and the sorption of organic pollutants on particulates with or without the presence of dissolved organic matters. By using this model, variations among the sorption equilibrium coefficients with the concentrations of dissolved organic matters are obtained. Also discussed herein are case studies involving pollutants having a wide spectrum of K(ow)s, different types of dissolved organic matters, different pH values and ionic strengths. In most of the case studies, the sorption equilibrium coefficients initially increase with the-concentrations of dissolved organic matters and, then, decrease after reaching a maximum value. This study also addresses the relative errors of partition coefficients attributed to the negligence of the effect caused by the dissolved organic matter, the so-called third-phase effect.

Journal Article↗

Chemical composition of sediments, suspended matter, river water and ground water of the Nile (Aswan-Sohag traverse).

Sediment, suspended matter, river water and ground water samples were collected at twelve sites in the drainage valley of the Nile River, around Sohag (Central Egypt) and close to the Aswan High Dam. Elemental composition of the river water (27 elements), ground water (eight elements), suspended matter (12 elements) and sediments (12 elements) was studied. Aswan High Dam construction, agricultural and industrial human activities have led to dramatic changes in the Nile River chemistry. Nowadays, the Nile River has the highest dissolved salt content among the major African rivers. Dissolved transport is a major process for Ca, K, Sr, Zn, Cu, Ni and V. Manganese, Fe and Cr are mainly carried by suspended matter. The Nile suspended matter is exhausted in almost all elements studied (except for Mn) compared to the world average river suspended matter. Along the course of the river, the distribution of elements in the suspended matter and sediments is generally controlled by natural processes: the relative importance of elemental transport phases; and the oxidation, precipitation and sedimentation of mineral species through the varying physico-chemical conditions of the environment. Pollution input in the Nile particulate load is not major, as compared to the natural inputs. Eight genetic particle types describe the composition of the Nile suspended matter and sediments: (1) biogenous-aeolian (or silica); (2) terrigenous (Fe-aluminosilicate); (3) authigenic (calcium carbonate); (4) biogenous (apatite); (5) authigenous-terrigenous (Fe-oxyhydroxide-montmorillonite); (6) diagenetic (iron-sulfide); (7) terrigenous (titanium oxide); (8) authigenous (Mn-Fe-oxyhydroxide).

Anions↗

Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study.

BACKGROUND: White-matter hyperintensities are commonly found on magnetic resonance imaging (MRI) of elderly people with or without dementia. Studies of the relation between severity of white-matter hyperintensities and cognitive impairment have had conflicting results. We undertook a longitudinal study of age-related decline in intellectual function and MRI at age 80 years. METHODS: From a cohort of 698 people born in 1914 and living in seven municipalities in Denmark, 68 healthy non-demented individuals had been tested with the Wechsler adult intelligence scale (WAIS) at ages 50, 60, and 70, and they agreed to further WAIS testing at age 80, and cerebral MRI at age 80-82 (mean age 82.3 years). We scored separately the numbers of periventricular and deep white-matter hyperintensities. FINDINGS: Scores for periventricular hyperintensities in this sample included all possible degrees of severity, but no participant scored more than 75% of maximum for deep white-matter hyperintensities. Neither type was related to the WAIS IQs of the 80-year assessment, but both were significantly associated with decline in performance IQ from age 50 to age 80 years (bivariate correlation coefficients 0.32, p=0.0087, and 0.28, p=0.0227, respectively). An analysis based on two WAIS subtests showed that the association between white-matter hyperintensities and cognitive impairment was significant only for cognitive decline in the decade 70-80 years. INTERPRETATION: Both periventricular and deep white-matter hyperintensities are related to decline in intelligence but, in healthy octogenarians, the cumulative effect of these features alone explains only a small part of the large differences among individuals in age-related decline in intelligence. Interpretation of the presence and severity of white-matter hyperintensities in a diagnostic context must be done cautiously.

Aged↗

White matter injury in the preterm infant: an important determination of abnormal neurodevelopment outcome.

Periventricular white matter injury, specifically cystic periventricular leukomalacia (PVL) and ipsilateral hemorrhage into white matter associated with periventricular-intraventricular hemorrhage (PV-IVH), contribute significantly to neonatal mortality and long-term neurodevelopmental deficits in the premature infant. The first lesion PVL occurs in approximately 3-4% of infants of birth weight (BW) < 1500 grams. It manifests either as a focal or diffuse lesion within white matter. Although the pathogenesis of PVL is complex and likely multifactorial, principle contributors include vascular factors which markedly increase the risk for ischemia during periods of systemic hypotension and the intrinsic vulnerability of the oligodendrocyte to neurotoxic factors such as free radicals or cytokines. Clinical associations with PVL include a history of chorioamnionitis, prolonged rupture of membranes, asphyxia, sepsis, hypocarbia, etc. The vast majority of infants exhibit long-term neurodevelopmental deficits that affect motor, cognitive and visual function. The second lesion, the ipsilateral hemorrhage into white matter lesion associated with PV-IVH, occurs in approximately 10-15% of infants of BW < 1000 grams. The white matter injury appears to be a venous infarction with hemorrhage occurring as a secondary phenomenon. Prevention of this lesion has to include prevention of the associated PV-IVH. In this regard, the antenatal administration of glucocorticoids has been associated with a significant reduction in the sonographic incidence of severe IVH and the associated white matter involvement. The postnatal administration of indomethacin to high risk infants appears to hold the most promise at the current time in preventing this lesion. The neurodevelopmental outcome with extensive white matter injury is universally poor, affecting long-term motor and cognitive deficits; the long-term outcome is more favorable with lesser involvement. A clearer understanding of pathogenesis of both conditions is essential so as to provide targeted preventative strategies.

Cerebral Hemorrhage↗

Anisotropic water diffusion in white and gray matter of the neonatal piglet brain before and after transient hypoxia-ischaemia.

Measurements of tissue water apparent diffusion coefficient (ADC) performed with diffusion sensitization applied separately along the x, y, and z axes revealed significant diffusion anisotropy in both cerebral white and gray matter in six newborn (< 24 h old) piglets. Mean baseline white matter ADC for a particular region of interest was 125.8% (SD 32.0%; p < .001) greater when the diffusion gradients were applied along the y axis as compared to along the x. For the cortical gray matter region considered, the situation was reversed, the mean ADC value measured along x exceeding that along y by 15.2% (SD 6.1%; p < .01). Forty-three hours subsequent to a transient cerebral hypoxic-ischaemic insult, phosphorous MRS measurements indicated that the animals had suffered severe secondary cerebral energy failure. This was accompanied by a significant (p < .01) decrease in the white matter anisotropy, such that the mean y direction ADC now exceeded that along the x by only 70.9% (SD 29.4%; p < .03). There was no change in the gray matter anisotropy. The average of the ADC values measured in the x, y, and z directions had decreased by 35.3% (SD 18.5%; p < .01) in white matter and 31.4% (SD 21.9%; p < .05) in cortical gray matter. Diffusion anisotropy measurements may provide additional information useful in the characterisation of hypoxic-ischaemic injury in the neonatal brain, and must be considered if tissue water ADC values are to be unambiguously interpreted in this context.

Animals↗

Glial cell changes in the white matter in temporal lobe epilepsy.

Temporal lobe gliosis and neuronal loss are pathological hallmarks of complex partial seizures. However, the specificity of glial cell changes is not clear. To assess this we studied surgically resected temporal lobes containing either medial temporal sclerosis (MTS) or temporal lobe epilepsy with tumour (TLET) and compared them with idiopathic epilepsy cases and normal controls. We quantitatively assessed glial cell density and mean nuclear volume in the white matter of various temporal gyri and the deep white matter. There was an increase in mean glial cell nuclear volume in MTS and TLET cases in the white matter of superior temporal gyrus, parahippocampal gyrus and deep white matter but not in the white matter of the middle temporal gyrus. In contrast, the densities of glial cells immunopositive for glial fibrillary acidic protein in the MTS and TLET groups were reduced in all white matter regions when compared with the controls. These changes may indicate that glial cells in the white matter have an active role to play in epilepsy pathogenesis.

Adolescent↗

Cortical gray matter deficit in patients with bipolar disorder.

BACKGROUND: cortical gray matter volume deficit and ventricular enlargement are well documented in schizophrenia, but their presence in bipolar disorder is less well established. METHODS: global cortical gray matter, white matter and sulcal CSF, as well as lateral and third ventricular volume measures, were derived from axial MRI brain images obtained on age-matched bipolar (n=9), schizophrenic (n=9), and control (n=16) subjects. All subjects were free of history of alcohol or other substance dependence. RESULTS: relative to controls, bipolar patients had widespread volume deficits of cortical gray matter but not of cortical white matter. Schizophrenic patients had an even more severe cortical gray matter deficit and greater sulcal and lateral ventricular enlargement than the bipolar patients. CONCLUSIONS: this group of patients with bipolar disorder had a widespread deficit of cortical gray matter similar to, but less pronounced than, that observed in patients with schizophrenia.

Adult↗

MR signal intensity of gray matter/white matter contrast and intracranial fat: effects of age and sex.

Signal intensity (SI) values of gray- and white-matter brain regions of interest (ROIs) were obtained from T(2)- and proton density-weighted magnetic resonance (MR) images of 58 normal subjects aged 22-82 years (31 females, 52.3+/-18.8 years; 27 males, 54.1+/-18.1 years). Sampled ROIs included the caudate, putamen, thalamus, orbitofrontal gyrus, gyrus rectus, uncus, frontal white matter, anterior and posterior corpus callosum, cranial-cervical junction fat, and retroorbital fat. Effects of age and sex on SI were examined using repeated-measures analysis of covariance. For both T(2)- and proton density-weighted acquisitions, a significant inverse relationship between age and SI was observed for the ratio of all summed gray-matter ROIs divided by summed white-matter ROIs. This relationship was additionally observed for ratios of both subcortical gray/white matter and cortical gray/white matter. Females compared with males had significantly lower cortical gray/white matter ratios on T(2)-weighted scans. Differences in SI were observed between cranial-cervical junction fat and retroorbital fat on both acquisitions, with females showing significantly higher values for cranial-cervical junction fat and males showing higher values for retroorbital fat. Implications for brain morphometry, the use of fat as a reference standard, and other issues in neuroimaging are discussed.

Adult↗

Role of Na(+)-Ca(2+) exchanger after traumatic or hypoxic/ischemic injury to spinal cord white matter.

BACKGROUND CONTEXT: Spinal cord injury is a devastating condition in which clinical disability results from demyelination of white matter tracts. Changes in glial-axonal signaling, and enhanced Ca(2+) channel activity with excessive accumulation of intracellular Ca(2+), is a common phenomenon after hypoxia/ischemia or mechanical trauma to spinal cord dorsal column white matter tracts leading to irreversible injury. PURPOSE: In the present study we examined the role of Na(+)-Ca(2+) exchanger (NCX) at physiological temperatures after hypoxia/ischemia and compressive injury to spinal cord dorsal column white matter in vitro. STUDY DESIGN: A 30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber (maintained at 37 degrees C) and injured by exposure to a hypoxic atmosphere for 60 minutes or compressed with a modified aneurysm clip (2-gm closing force) for 15 seconds. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential (CAP) with glass microelectrodes. RESULTS: The mean CAP decreased to 49.5 +/- 5.7% and 49.4 +/- 2.6% of control (p<.05) after hypoxia/ischemia and compressive injury, respectively. KB-R7943, a potent, selective NCX reverse mode inhibitor, significantly promoted greater recovery of CAP amplitude to 82.0 +/- 10.0% and 70.8 +/- 10.7% of control (p<.05) after hypoxic/ischemic or compressive injury to dorsal column white matter, respectively, when applied at 10 microM concentration. Bepridil (Research Biochemical Inc., Natick, MA, USA) (a less selective NCX inhibitor), when applied at 10 microM and 50 microM concentration promoted CAP amplitude recovery only to 46.8 +/- 7.8% and 29.9 +/- 3.3% of control, respectively, after hypoxic/ischemic injury to dorsal column white matter. Western blot analysis identified NCX presence with positive immunolabeling of 160 kD and 120 kD NCX proteins in the spinal cord white matter. CONCLUSION: In conclusion, at physiological temperature NCX activation plays an important role in intracellular calcium overload after hypoxic/ischemic and compressive injury to spinal cord dorsal column white matter in vitro.

Animals↗

Organic matter in central California radiation fogs.

Organic matter was studied in radiation fogs in the San Joaquin Valley of California during the California Regional Particulate Air Quality Study (CRPAQS). Total organic carbon (TOC) concentrations ranged from 2 to 40 ppm of C. While most organic carbon was found in solution as dissolved organic carbon (DOC), 23% on average was not dissolved inside the fog drops. We observe a clear variation of organic matter concentration with droplet size. TOC concentrations in small fog drops (<17 microm) were a factor of 3, on average, higher than TOC concentrations in larger drops. As much as half of the dissolved organic matter was determined to have a molecular weight higher than 500 Da. Deposition fluxes of organic matter in fog drops were high (0.5-4.3 microg of C m(-2) min(-1)), indicating the importance of fog processing as a vector for removal of organic matter from the atmosphere. Deposition velocities of organic matter, however, were usually found to be lower than deposition velocities for fogwater, consistent with the enrichment of the organic matter in smaller fog drops with lower terminal settling velocities.

Air Movements↗

Clinical characteristics of children with cerebral white matter abnormalities.

The rapidly expanding use of magnetic resonance imaging (MRI) in children with neurological impairments of unknown aetiology has revealed a large number of children with abnormalities of the cerebral white matter, some with leukodystrophy-like white matter abnormalities on MRI, but non-progressive in clinical presentation and course. The aim of this study was to investigate the clinical and neuroradiological characteristics of 26 children with white matter abnormalities of unknown origin and to find diagnostic clues or indicators of progressive versus nonprogressive disease. The typical child with white matter abnormalities was characterized by onset of symptoms within the first year of life, most often presenting as general developmental delay and hypotonia. Later-appearing signs were spasticity and ataxia and as a rule severe learning and motor disabilities. Serious ophthalmological signs were frequently seen. Perinatal adverse events were rare, infectious aetiologies not indicated but prenatal stigmata relatively common. The clinical course was progressive in 11 children and non-progressive in 15. Late onset presentation was associated with a progressive course whereas prenatal stigmata and asymmetrical white matter lesions only were found in children with a non-progressive disorder. The MRI showed three main patterns: a) a generalized increase of the T2 signal of the white matter in 12 children, b) a bilateral, symmetric but not generalized abnormality in nine and c) asymmetric, focal or multifocal pathology in five. Useful information as to clinical entities and course was obtained from the combined clinical and radiological assessment. A precise nosological diagnosis could be made in six cases. The study showed that white matter abnormalities in children constitute a heterogeneous group of rare and 'anonymous' conditions, motivating collaborative studies for further clarification of background and management.

Adolescent↗

White matter abnormalities in tuberous sclerosis complex.

PURPOSE: The aim of this study was to investigate and describe the range of white matter abnormalities in children with tuberous sclerosis complex by means of MR imaging. MATERIAL AND METHODS: A retrospective cross-sectional study was performed on the basis of MR imaging findings in 20 cases of tuberous sclerosis complex in children aged 17 years or younger. RESULTS: White matter abnormalities were present in 19/20 (95%) cases of tuberous sclerosis complex. These were most frequently (19/20 cases) found in relation to cortical tubers in the supratentorial compartment. White matter abnormalities related to tubers were found in the cerebellum in 3/20 (15%) cases. White matter abnormalities described as radial migration lines were found in relation to 5 tubers in 3 (15%) children. In 4/20 (20%) cases, white matter abnormalities were found that were not related to cortical tubers. These areas had the appearance of white matter cysts in 3 cases and infarction in the fourth. In the latter case there was a definable event in the clinical history, supporting the diagnosis of stroke. CONCLUSION: A range of white matter abnormalities were found by MR imaging in tuberous sclerosis complex, the commonest being gliosis and hypomyelination related to cortical tubers. Radial migration lines were seen infrequently in relation to cortical tubers and these are thought to represent heterotopic glia and neurons along the expected path of cortical migration.

Adolescent↗

Application of the IAS theory combining to a three compartments description of natural organic matter to the adsorption of atrazine or diuron on activated carbon.

The study of natural organic matter (NOM) adsorption on an activated carbon showed that equilibrium cannot be described according to a simple model such as a Freundlich isotherm and confirms the need for a closer description of the organic matter to simulate the competitive adsorption with micropollutants. A representation of the organic matter in three fractions is chosen: non-adsorbable, weak and strong adsorbable. The Ideal Adsorbed Solution Theory (IAST) can, under restrictive conditions, be used to effectively predict the competition between the pesticides and the organic matter. Therefore, it was noted that the model simulated with good precision the competition between atrazine or diuron and natural organic matter in aqueous solution for two activated carbons (A and B). The same parameters for the modeling of organic matter adsorption (Freudlich constants for two absorbable fractions) are used with the two pesticides. However, IAST does not allow correct modeling of pesticide adsorption onto two other (C and D) activated carbons in solution in natural water to be described. IAS theory does not reveal competition between diuron and NOM and pore blockage mechanism by the NOM is proposed as the major effect for the adsorption capacity reduction. However, the difference observed between the two pesticides could be due to in addition to the pore blockage effect, a particular phenomenon with the diuron, especially with D activated carbon. We can suppose specific interactions between the diuron and the adsorbed organic matter and a competition between adsorption sites of NOM and activated carbon surface.

Adsorption↗

The role of ozonation and activated carbon filtration in the natural organic matter removal from drinking water.

Aquatic natural organic matter is one of the most important problems in the drinking water treatment process design and development. In this study, the removal of the natural organic matter was followed both in the full-scale drinking water treatment process and in the pilot-scale studies. The full-scale process consisted of coagulation, flocculation and flotation, sand filtration, ozonation, activated carbon filtration and disinfection. The aim of the pilot study was to investigate the influence of the dose and contact time of ozonation, and also the impact of activated carbon filtration, on the removal efficiency of organic matter. Several methods, including high-performance size-exclusion chromatography, total organic carbon content and assimilable organic carbon content measurements were used to characterize the behaviour of organic matter and its removal efficiency. On the full-scale process, total organic carbon was removed by over 90 %. According to size-exclusion measurements, chemical coagulation removed the high molar mass organic matter with an efficiency of 98%. The ozonation further removed the smaller molar mass fraction compounds by about 27%, while residual higher molar mass matter remained quite unaltered. Activated carbon filtration removed primarily intermediate and low molar mass organic matter. In the pilot-tests, conducted with sand filtered water from the full-scale process, it was noticed, that the ozonation removed primarily smaller organic compounds. The amount of assimilable organic carbon increased with increasing ozone dose, up to 0.4 mg l(-1) with the highest ozone dose of 4.0 mg 1(-1). The activated carbon filtration removed the assimilable organic carbon. Total organic carbon content was not reduced in ozonation.

Carbon↗

White matter changes in dementia of Alzheimer's type. Biochemical and neuropathological correlates.

A correlative neuropathological-biochemical study was undertaken in order to characterize the selective incomplete white matter infarctions (SIWI) frequently found in dementia of Alzheimer's type. The brain tissue analysed represented white matter with incomplete infarction, complete infarcts and with histologically normal tissue, in cases with dementia, mainly of Alzheimer and multi-infarct type, in nondemented subjects with cerebral infarcts and in age-matched control cases. The biochemical results verify the existence of the white matter changes and agree on their regional distribution as they appear in the morphological analyses. The increasing severity of SIWI as assessed histologically was reflected in a proportional reduction of several biochemically quantified white matter components. The histological difference between incomplete and complete infarction was also expressed biochemically. Incomplete white matter infarction with and without associated complete infarcts were biochemically similar. The aetiological significance of the loss of different white matter components is discussed. The biochemical data support the concept of SIWI as being an independent white matter disorder of cerebrovascular, hypoperfusional/hypoxic origin.

Aged↗