Pathological changes in the primary visual cortex (area V1) in sporadic Creutzfeldt-Jakob disease

Purpose. To determine the degree of pathological change in the primary visual cortex (area V1) in patients with Creutzfeldt-Jakob disease. Method. The vacuolation, surviving neurons, glial cells, and deposits of prion protein were quantified in area V1 obtained postmortem in nine cases of the sporadic type of Creutzfeldt-Jakob disease. Results. Variations in the density of glial cells and in prion protein deposition were particularly evident between patients. In the upper and lower cortical laminae, vacuoles and prion protein deposits were regularly distributed in clusters with a mean dimensions of 450 to 1000 µm. Vacuolation in area V1 was most severe in lamina III and the glial cell reaction in lamina V or VI. Surviving neurons were most abundant in lamina II or III, whereas prion protein deposition either affected all laminae equally or was maximal in lamina II or III. Conclusion. The data suggest that pathological changes in area V1 in sporadic type of Creutzfeldt-Jakob disease may affect the transmission of visual information from area V1 to V2 and to subcortical visual areas. In addition, the data suggest an association between the developing pathology and the functional domains of area V1.

Laminar distribution of the pathological changes in the cerebral cortex in variant Creutzfeldt-Jakob disease (vCJD)

To determine the pattern of cortical degeneration in cases of variant Creutzfeldt-Jakob disease (vCJD), the laminar distribution of the vacuolation ("spongiform change"), surviving neurones, glial cell nuclei, and prion protein (PrP) deposits was studied in the frontal, parietal and temporal lobes. The vacuolation exhibited two common patterns of distribution: either the vacuoles were present throughout the cortex or a bimodal distribution was present with peaks of density in the upper and lower cortical laminae. The distribution of the surviving neurones was highly variable in different regions; the commonest pattern being a uniform distribution with cortical depth. Glial cell nuclei were distributed largely in the lower cortical laminae. The non-florid PrP deposits exhibited either a bimodal distribution or exhibited a peak of density in the upper cortex while the florid deposits were either uniformly distributed down the cortex or were present in the upper cortical laminae. In a significant proportion of areas, the density of the vacuoles was positively correlated with either the surviving neurones or with the glial cell nuclei. These results suggest similarities and differences in the laminar distributions of the pathogenic changes in vCJD compared with cases of sporadic CJD (sCJD). The laminar distribution of vacuoles was more extensive in vCJD than in sCJD whereas the distribution of the glial cell nuclei was similar in the two disorders. In addition, PrP deposits in sCJD were localised mainly in the lower cortical laminae while in vCJD, PrP deposits were either present in all laminae or restricted to the upper cortical laminae. These patterns of laminar distribution suggest that the process of cortical degeneration may be distinctly different in vCJD compared with sCJD.

Spatial patterns of the vacuolation in subcortical white matter in sporadic Creutzfeldt-Jakob disease (sCJD)

OBJECTIVE: To study the spatial patterns of the vacuolation ("spongiform change") in the subcortical white matter in the "classical" form of sporadic Creutzfeldt-Jakob disease (sCJD). MATERIAL: Frontal, parietal, occipital and temporal lobes of 11 cases of sCJD. METHOD: Spatial patterns were studied across the white matter at the base of the gyri using spatial pattern analysis. RESULTS: In the white matter of all gyri studied, vacuoles were aggregated into clusters, 50 to > 800 microm in diameter and in 22/37 (59%) of gyri, the clusters of vacuoles exhibited a regular distribution across the base of the gyri. In the remaining gyri, the vacuoles were aggregated into large clusters, at least 400 microm or 800 microm in diameter, but without evidence of a regular distribution. In a significant proportion of gyri, the spatial patterns of the vacuolation were similar to those reported previously for spongiform change and prion protein (PrP) deposits in the corresponding grey matter. CONCLUSIONS: Degeneration of the white matter and the formation of clusters of vacuoles may occur before the degeneration of the grey matter or could be a consequence of pathology affecting the cortico-cortical pathways.

Correlations between the clustering patterns of the pathological changes in sporadic Creutzfeldt-Jakob disease

Correlations between the clustering patterns of the vacuolation ('spongiform change'), prion protein (PrP) deposits, and surviving neurons were studied in the cerebral cortex, hippocampus, and cerebellum in 11 cases of sporadic Creutzfeldt-Jakob disease (sCJD). Differences in the sizes of the clusters of vacuoles were observed between brain regions and in the cerebral cortex, between the upper and lower laminae. With the exception of the parietal cortex, mean cluster size of the vacuoles was similar to that of the PrP deposits in each brain area. Clusters of the vacuoles were spatially correlated with the density of surviving neurons and with the clusters of PrP deposits in 47% and 53% of cortical areas analysed respectively but there were few spatial correlation between the PrP deposits and the density of surviving neurons. The data suggest that the pathology of sCJD may spread through the brain via specific anatomical pathways. Development of the clusters of vacuoles is spatially related to surviving neurons while the appearance of clusters of PrP deposits is related to the development of the vacuolation.

Laminar distribution of the pathological changes in sporadic and variant Creutzfeldt-Jakob disease

The laminar distributions of the pathological changes in the cerebral cortex were compared in the prion diseases sporadic Creutzfeldt-Jakob disease (sCJD) and variant CJD (vCJD). First, in some cortical regions the vacuolation (‘spongiform change’) was more generally distributed across the cortex in sCJD. Second, there was greater neuronal loss in the upper cortex in vCJD and in the lower cortex in sCJD. Third, the ‘diffuse’ and ‘florid’ prion protein (PrPsc) deposits were more frequently distributed in the upper cortex in vCJD and the ‘synaptic’ deposits in the lower cortex in sCJD. Fourth, there was a significant gliosis mainly affecting the lower cortex of both disorders. The data suggest that the pattern of cortical degeneration is different in sCJD and vCJD which may reflect differences in aetiology and the subsequent spread of prion pathology in the brain.

Pathological changes in the sporadic and variant forms Of Creutzfeldt-Jakob Disease (CJD) are spatially related to blood vessels

The objective of this article was to determine whether the pathological changes of Creutzfeldt-Jacob disease (CJD) were related to the brain microcirculation. Hence, the spatial correlations between the vacuolation, prion protein (PrP) deposits, and the blood vessel profiles were studied in immunolabelled sections of the cerebral cortex, hippocampus, and cerebellum in two subtypes of CJD, viz., sporadic CJD (sCJD) and variant CJD (vCJD). In sCJD, both the vacuolation and the ‘synaptic-type’ PrP deposits were spatially correlated with the microvessels; the PrP deposits being more strongly correlated than the vacuoles. In vCJD, there were no significant spatial correlations between either the vacuolation or the diffuse-type of PrP deposit and the microvessels. By contrast, a consistent pattern of spatial correlation was observed in gyri of the cerebral cortex between the florid PrP deposits and microvessels. In both sCJD and vCJD, the frequency of positive spatial correlations was similar in the different gyri of the cerebral cortex and in the upper compared with the lower laminae. In conclusion, the microcirculation may be more significantly involved in determining the pathological changes in sCJD than in vCJD. The spatial correlations of the florid PrP deposits in vCJD and the synaptic deposits in sCJD and the blood vessels may be attributable to factors associated with the microcirculation which enhance the aggregation of PrP molecules rather than representing a possible haematogenous spread of the disease. S

Quantitative variations in the pathology of 11 cases of variant Creutzfeldt-Jakob disease (vCJD)

Quantitative variations in the density and distribution of the vacuolation ('spongiform change'), surviving neurons, and prion protein (PrP) deposits were studied in eight brain regions from 11 cases of variant Creutzfeldt-Jakob disease (vCJD). Principal components analysis (PCA) was used to study the similarities and differences between cases and to identify the neuropathological variables which could best account for these variations. Two principal components (PC) were extracted from the data accounting in total for 93.4% of the variance; the majority of the variance (90%) being associated with PC1. Some clustering of the 11 cases in relation to PC1 and PC2 was evident. The densities of the vacuolation in the occipital cortex and the molecular layer of the cerebellum were positively and negatively correlated, respectively, with PC1. No significant variation between cases was associated with PrP deposition. These data suggest that vCJD cases have a consistent neuropathological profile characterised by the presence of vacuolation, neuronal loss and PrP deposition in the form of florid and non-florid deposits. However, there are quantitative variations between cases in the development of the vacuolation especially affecting the occipital cortex and cerebellum. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

The spatial pattern of the vacuolation in patients with sporadic Creutzfeldt-Jakob disease

The spatial pattern of the vacuolation ('spongiform change') was studied in the upper and lower laminae of the cerebral cortex, the CA1/CA2 sectors of the hippocampus and the molecular layer of the cerebellum in 11 cases of sporadic Creutzfeldt-Jakob disease (CJD). Individual vacuoles were grouped into clusters, 50 to >1600 μm in diameter and, in the majority of tissue sections, the vacuole clusters were distributed with regular periodicity parallel to the tissue boundary. The size of the vacuole clusters was positively correlated with patient age in the lower laminae of the occipital cortex and the inferior temporal gyrus (ITG) and negatively correlated with age in the hippocampus. In addition, the size of the vacuole clusters was positively correlated with disease duration in the upper laminae of the ITG. The size and distribution of the vacuole clusters suggests that the vacuolation in CJD reflects the degeneration of specific brain pathways and supports the hypothesis that prion pathology may spread through the brain along well defined anatomical pathways. (C) 2000 Elsevier Science Ireland Ltd.

Getting your proteins in a twist: disease caused by prions

In recent years, a number of diseases caused by proteinaceous agents caused prions have been described. This article describes the nature of prions, how prions may cause disease, and the symptoms and pathology associated with prion diseases.

Creutzfeldt-Jakob disease and vision

This article describes the symptoms and pathology associated with Creutzfeldt-Jakob disease and prion disease, how prion protein may cause disease and the visual aspects of prion diseases.

Variant Creutzfeldt-Jakob disease and the eye

Variant Creutzfeldt-Jakob disease (vCJD) was first described in the UK in 1996 and is one of a group of diseases, the transmissible spongiform encephalopathies (TSEs) which affect both animals and humans. This review discusses vCJD in the context of other TSEs, considers the controversial 'prion' hypothesis as to the cause of the disease, the ocular features of vCJD, and the possible transmission of the disease via optoetric devices.

A quantitative study of the pathological changes in the cortical white matter in variant Creutzfeldt-Jakob disease (vCJD)

The objective of this study was to determine the degree of white matter pathology in the cerebral cortex in cases of variant Creutzfeldt-Jakob disease (vCJD) and to study the relationships between the white matter and grey matter pathologies. Hence, the pathological changes in cortical white matter were studied in individual gyri of the frontal, parietal, occipital, and temporal cortex in eleven cases of vCJD. Vacuolation (‘spongiform change’), deposition of the disease form of prion protein (PrPsc) in the form of discrete PrP deposits, and gliosis were observed in the white matter of virtually all cortical regions studied. Mean density of the vacuoles in the white matter was greater in the parietal lobe compared with the frontal, occipital, and temporal lobes but there were fewer glial cells in the occipital lobe compared with the other cortical regions. In the white matter of the frontal cortex, vacuole density was negatively correlated with the density of both glial cell nuclei and the PrP deposits. In addition, the densities of glial cells and PrP deposits were positively correlated in the frontal and parietal cortex. In the white matter of the frontal cortex and inferior temporal gyrus, there was a negative correlation between the densities of the vacuoles and the number of surviving neurons in laminae V/VI of the adjacent grey matter. In addition, in the frontal cortex, vacuole density in the white matter was negatively correlated with the density of the diffuse PrP deposits in laminae II/III and V/VI of the adjacent grey matter. The densities of PrP deposits in the white matter of the frontal cortex were positively correlated with the density of the diffuse PrP deposits in laminae II/III and V/V1 and with the number of surviving neurons in laminae V/V1. The data suggest that in the white matter in vCJD, gliosis is associated with the development of PrP deposits while the appearance of the vacuolation is a later development. In addition, neuronal loss and PrP deposition in the lower cortical laminae of the grey matter may be a consequence of axonal degeneration within the white matter.

Creutzfeldt-Jakob disease and the eye

This article describes: 1) the symptoms and pathology of CJD, 2) how prion proteins may cause CJD, 3) the visual signs and symptoms of CJD, and 4) the scientific evidence which supports a possible transmission of CJD via optometric devices.

A quantitative study of the pathological changes in the cortical white matter in variant Creutzfeldt-Jakob disease (vCJD).

Objective: To quantify cortical white matter pathology in variant Creutzfeldt-Jakob disease (vCJD) and to correlate white and grey matter pathologies. Methods: Pathological changes were studied in immunolabeled sections of the frontal, parietal, occipital, and temporal cortex of eleven cases of vCJD. Results: Vacuolation ("spongiform change"), deposition of the disease form of prion protein (PrPsc), and a glial cell reaction were observed in the white matter. The density of the vacuoles was greatest in the white matter of the occipital cortex and glial cell density in the inferior temporal gyrus (ITG). Florid-type PrPsc deposits were present in approximately 50% of white matter regions studied. In the white matter of the frontal cortex (FC), vacuole density was negatively correlated with the densities of both glial cell nuclei and PrPsc deposits. In addition, in the frontal and parietal cortices the densities of glial cells and PrPsc deposits were positively correlated. In the FC and ITG, there was a negative correlation between the densities of the vacuoles in the white matter and the number of surviving neurons in laminae V/VI of the adjacent grey matter. In the FC, vacuole density in the white matter was negatively correlated with the density of the diffuse PrPsc deposits in laminae II/III and V/VI of the adjacent grey matter. In addition, the densities of PrPsc deposits in the white matter of the FC were positively correlated with the density of the diffuse PrPsc deposits in laminae II/III and V/VI and with the number of surviving neurons in laminae V/VI. Conclusion: The data suggest significant degeneration of cortical white matter in vCJD; the vacuolation being related to neuronal loss in the lower cortical laminae of adjacent grey matter, PrPsc deposits the result of leakage from damaged axons, and gliosis a reaction to these changes.

Pathological changes in the sporadic and variant forms of Creutzfeldt-Jakob Disease (CJD) are spatially related to blood vessels

The objective of this article was to determine whether the pathological changes of Creutzfeldt-Jacob disease (CJD) were related to the brain microcirculation. Hence, the spatial correlations between the vacuolation, prion protein (PrP) deposits, and the blood vessel profiles were studied in immunolabelled sections of the cerebral cortex, hippocampus, and cerebellum in two subtypes of CJD, viz., sporadic CJD (sCJD) and variant CJD (vCJD). In sCJD, both the vacuolation and the ‘synaptic-type’ PrP deposits were spatially correlated with the microvessels; the PrP deposits being more strongly correlated than the vacuoles. In vCJD, there were no significant spatial correlations between either the vacuolation or the diffuse-type of PrP deposit and the microvessels. By contrast, a consistent pattern of spatial correlation was observed in gyri of the cerebral cortex between the florid PrP deposits and microvessels. In both sCJD and vCJD, the frequency of positive spatial correlations was similar in the different gyri of the cerebral cortex and in the upper compared with the lower laminae. In conclusion, the microcirculation may be more significantly involved in determining the pathological changes in sCJD than in vCJD. The spatial correlations of the florid PrP deposits in vCJD and the synaptic deposits in sCJD and the blood vessels may be attributable to factors associated with the microcirculation which enhance the aggregation of PrP molecules rather than representing a possible haematogenous spread of the disease.