Gray Matter In Patients Research Articles

Unbiased whole-brain analysis of gray matter loss in Alzheimer's disease

In patients with Alzheimer's disease, substantial tissue loss occurs in the medial temporal lobe. In this study, we applied a voxel-based, unbiased whole-brain analysis method to compare magnetic resonance imaging scans of seven patients with Alzheimer's disease and seven healthy elderly controls. Images were transformed to standard coordinate space and tested for gray matter loss in patients. We found symmetrical decreases of gray matter in patients in the hippocampus, and, unexpectedly, also in the head of the caudate nucleus and the insula. The exact role of these two structures in the symptomatology of Alzheimer's disease deserves further attention.

Blood-Brain Barrier Tight Junction Disruption in Human Immunodeficiency Virus-1 Encephalitis

The blood-brain barrier (BBB) plays a critical role in regulating cell trafficking through the central nervous system (CNS) due to several unique anatomical features, including the presence of interendothelial tight junctions that form impermeable seals between the cells. Previous studies have demonstrated BBB perturbations during human immunodeficiency virus encephalitis (HIVE); however, the basis of these permeability changes and its relationship to infiltration of human immunodeficiency virus type 1 (HIV-1)-infected monocytes, a critical event in the pathogenesis of the disease, remains unclear. In this study, we examined CNS tissue from HIV-1-seronegative patients and HIV-1-infected patients, both with and without encephalitis, for alterations in BBB integrity via immunohistochemical analysis of the tight junction membrane proteins, occludin and zonula occludens-1 (ZO-1). Significant tight junction disruption (P < 0.001), as demonstrated by fragmentation or absence of immunoreactivity for occludin and ZO-1, was observed within vessels from subcortical white matter, basal ganglia, and, to a lesser extent, cortical gray matter in patients who died with HIVE. These alterations were also associated with accumulation of activated, HIV-1-infected brain macrophages, fibrinogen leakage, and marked astrocytosis. In contrast, no significant changes (P > 0.05) were observed in cerebellar tissue from patients with HIVE compared to HIV-seronegative patients or HIV-1-infected patients without encephalitis. Our findings demonstrate that tight junction disruption is a key feature of HIVE that occurs in regions of histopathological alterations in association with perivascular accumulation of activated HIV-1-infected macrophages, serum protein extravasation, and marked astrocytosis. We propose that disruption of this key BBB structure serves as the main route of HIV-1-infected monocyte entry into the CNS.

Incidence of ectopic gray matter in patients with schizophrenia and healthy control subjects studied with MRI.

Magnetic resonance imaging scans were visually inspected to investigate the incidence of gray matter heterotopia (GMH) in a group of 55 schizophrenic patients and a group of 75 control subjects. No GMHs were found in the control subjects. In the patient group, 1 GMH was found, an incidence of 1.8%.

Pathology of the cerebellar dentate nucleus in sporadic olivopontocerebellar atrophy: a morphometric investigation

The pathology of the cerebellar dentate nucleus was investigated by morphometric methods in three patients with sporadic olivopontocerebellar atrophy (sOPCA), and the results were compared to specimens from three subjects without neurological disease (controls). The size of dentate neurons; the number of small and large neurons (50–199 μm 2 and larger than 200 μm 2, respectively) at rostral, middle, and caudal levels; nerve cell density; total volume of the gray band; and total nerve cell number, were estimated with an image analyzer applied to serial 20-μm-thick sections of one celloidin-embedded cerebellar hemisphere. The number of small neurons in patients with sOPCA was significantly increased at the rostral level while the number of large neurons showed large inter-individual variations. Dentate neurons also showed various qualitative changes such as atrophy and hypertrophy. The nerve cell density in the dentate nucleus was 1.7 times higher in the patients than in the controls. However, the total volume of the gray band was reduced to one-half of that in controls. There were no differences in the total nerve cell number between the patients and controls. This reduction in size of the dentate gray matter in patients with sOPCA may result from the disappearance of afferent nerve fibers originating from Purkinje cells, inferior olivary neurons, and pontine neurons.

PET, CT, and MRI Imaging of Neuronal Migration Anomalies in Epileptic Patients

During the investigation of intractable epilepsy, neuronal migration anomalies [NMA] were discovered in three patients. The first patient had abnormally positioned gray matter within the walls of both lateral ventricles. The second patient had a post operative cystic area in the right parietal-occipital lobes and an area of NMA within the right temporal lobe. The third patient had abnormally thickened gray matter in the right operculum. Long term CCTV-EEG monitoring of these three patients revealed ictal discharges originating from the area of abnormal gray matter in patients 2 and 3. PET scanning showed the areas of NMA in all three patients to have similar metabolic activity to normal gray matter. These cases illustrate the value of various imaging modalities and suggest some interesting physiology of a spectrum of neuronal migration anomalies.

Local cerebral blood flow and partition coefficients measured in cerebral astrocytomas of different grades of malignancy

Local cerebral blood flow and local partition coefficients were measured in patients with different grades of malignant cerebral astrocytomas (n=5) who inhaled 35% stable xenon during computed tomography scanning. Results were compared with those in age-matched normal subjects (n = 5). Mean values for local cerebral blood flow in the gray matter in patients with astrocytomas were decreased throughout the tumor mass and surrounding brain that was apparently free of tumor. Patients with highly malignant glioblastoma multiforme (astrocytoma grade IV; n=2) showed more variable values for local cerebral blood flow and local partition coefficients compared to those with astrocytomas of lower grades (grades I-II; n = 3). Local partition coefficients in gray matter invaded by grade IV astrocytoma were significantly higher than those in gray matter invaded by grade I-III astrocytomas. Local cerebral blood flow and local partition coefficients in the brain tissue surrounding grade IV astrocytomas were reduced to a greater extent than those in more benign tumors.

Direct NMR—Imaging of true flow in humans

NODDI (Neurite Orientation Dispersion and Density Imaging) and DTI (Diffusion tensor imaging) may be useful in identifying abnormal regions in patients with MRI-negative refractory epilepsy. The aim of this study was to determine whether NODDI and DTI maps including neurite density (ND), orientation dispersion index (ODI), mean diffusivity (MD) and fractional anisotropy (FA) can detect structural abnormalities in cortical and subcortical gray matter (GM) in these patients. The correlation between these parameters and clinical characteristics of the disease was also investigated.NODDI and DTI maps of 17 patients were obtained and checked visually. Region of interest (ROI) was drawn on suspected areas and contralateral regions in cortex. Contrast-to-noise ratio (CNR) was determined for each region. Furthermore volumetric data and mean values of ND, ODI, FA and MD of subcortical GM structures were calculated in both of the patients and controls. Finally, the correlations of these parameters in the subcortical with age of onset and duration of epilepsy were investigated.Cortical abnormalities on ODI images were observed in eight patients qualitatively. CNR of ODI was significantly greater than FA and MD. The subcortical changes including decrease of FA and ND and increase of ODI in left nucleus accumbens and increase of the volume in right amygdala were detected in the patients.The results revealed that NODDI can improve detection of microstructural changes in cortical and subcortical GM in patients with MRI negative epilepsy.

Brain ceramide hexosides in Tay-Sachs disease and generalized gangliosidosis (GM1-gangliosidosis)

The carbohydrate composition was determined for ceramide hexosides isolated from brains of patients with Tay-Sachs disease and generalized gangliosidosis (hereby named GM1-gangliosidosis). Gray matter of patients with each disease showed a characteristic abnormal ceramide hexoside pattern. In Tay-Sachs gray matter, ceramide trihexoside is the major component, whereas ceramide tetrahexoside is barely detectable. In GM1-gangliosidosis, ceramide tetrahexoside is the major ceramide hexoside, while ceramide trihexoside is present only in small amount. These two major components have been characterized as the asialo derivatives of, respectively, the "Tay-Sachs ganglioside" (GM2-ganglioside) and the normal major monosialoganglioside (GM1-ganglioside). In both diseases, more than half the ceramide monohexoside of gray matter was glucocerebroside. Gray matter ceramide dihexoside, present in both diseases at higher than normal levels, was mostly ceramide lactoside, with possibly a small amount of ceramide digalactoside. Sulfatide contained only galactose. The abnormal ceramide hexoside pattern is limited to gray matter: white matter showed normal ceramide hexosides, i.e. a preponderance of monohexosides and sulfatide, with no detectable glucocerebroside.