Multiple system atrophy: laminar distribution of the pathological changes in frontal and temporal neocortex--a study in ten patients

OBJECTIVE: To determine the distribution of the pathological changes in the neocortex in multiple-system atrophy (MSA). METHOD: The vertical distribution of the abnormal neurons (neurons with enlarged or atrophic perikarya), surviving neurons, glial cytoplasmic inclusions (GCI) and neuronal cytoplasmic inclusions (NI) were studied in alpha-synuclein-stained material of frontal and temporal cortex in ten cases of MSA. RESULTS: Abnormal neurons exhibited two common patterns of distribution, viz., density was either maximal in the upper cortex or a bimodal distribution was present with a density peak in the upper and lower cortex. The NI were either located in the lower cortex or were more uniformly distributed down the cortical profile. The distribution of the GCI varied considerably between gyri and cases. The density of the glial cell nuclei was maximal in the lower cortex in the majority of gyri. In a number of gyri, there was a positive correlation between the vertical densities of the abnormal neurons, the total number of surviving neurons, and the glial cell nuclei. The vertical densities of the GCI were not correlated with those of the surviving neurons or glial cells but the GCI and NI were positively correlated in a small number of gyri. CONCLUSION: The data suggest that there is significant degeneration of the frontal and temporal lobes in MSA, the lower laminae being affected more significantly than the upper laminae. Cortical degeneration in MSA is likely to be secondary to pathological changes occurring within subcortical areas.

Lobe interactions within the thallus margin and the maintenance of symmetry in the lichen Parmelia conspersa (Ehrh. ex Ach.)Ach.

This study determined whether the radial growth of lobes of the foliose lichen Parmelia conspersa (Ehrh. ex Ach.)Ach. was influenced by the radial growth and morphology of their closest neighbours and whether such interactions influence thallus symmetry. The radial growth and morphology of a sample of adjacent lobes from six thalli was measured. Positive correlations were observed between radial growth and lobe width in three thalli and with the degree of bifurcation of the lobe in two thalli. Negative correlations between the radial growth of adjacent lobes were observed in four thalli suggesting that faster growing lobes may inhibit the growth of their neighbours.Lobes glued next to individual lobes had no signifiacnt effect on the radial growth of wide or narrow lobes. Lobes glued 1-2 mm in front of their neighbours exhibited an intital phase of increased radial growth and then a phase of slower growth. Radial growth decreased when the lobes were glued 2 mm behind their neighbours and these lobes were essentially eliminated by the growth of the adjacent lobes. The data suggest that lobe interactions may incresae lobe growth variation within a thallus. However, the decrease in radial growth of lobes which protrude from the margin and the elimination of slower growing lobes may help to maintain thallus symmetry.

Beta-amyloid deposition in the temporal lobe of patients with dementia with Lewy bodies:Comparison with non-demented cases and Alzheimer's disease

β-Amyloid (Aβ) deposition in regions of the temporal lobe in patients with dementia with Lewy bodies (DLB) was compared with elderly, non-demented (ND) cases and with Alzheimer's disease (AD). The distribution, density and clustering patterns of diffuse, primitive and classic Aβ deposits were similar in 'pure' DLB and ND cases. The distribution of Aβ deposits and the densities of the diffuse and primitive deposits were similar in 'mixed' DLB/AD cases compared with AD. However, the density of the classic deposits was significantly lower in DLB/AD compared with AD. In addition, the primitive Aβ deposits occurred more often in small, regularly spaced clusters in the tissue and less often in a single large cluster in DLB/AD compared with 'pure' AD. These results suggest that pure DLB and AD are distinct disorders which can coexist in some patients. However, the Aβ pathology of DLB/AD cases is not identical to that observed in patients with AD alone. (C) 2000 S. Karger AG, Basel.

A quantitative study of the pathological lesions in the neocortex and hippocampus of twelve patients with corticobasal degeneration

The density of ballooned neurons (BN), tau-positive neurons with inclusion bodies (tau+ neurons), and tau-positive plaques (tau+ plaques) was determined in sections of the frontal, parietal, and temporal lobe in 12 patients with corticobasal degeneration (CBD). No significant differences in the mean density of BN and tau+ neurons were observed between neocortical regions. In the hippocampus, the densities of BN were significantly lower than in the neocortex, and densities of tau+ neurons were greater in sectors CA1 and CA2, compared with CA3 and CA4. Tau+ plaques were present in one or more brain regions in six patients. Significantly more BN were recorded in the lower (laminae V/VI) compared with the upper cortex (laminae I/II/III) but tau+ neurons were equally frequent in the upper and lower cortex. No significant correlations were observed between the densities of BN and tau+ neurons, but the densities of BN in the superior temporal gyrus and tau+ plaques in the frontal cortex were positively correlated with age. A principal components analysis (PCA) suggested that differences in the density of tau+ neurons in the frontal and motor cortex were the most important sources of variation between patients. In addition, one patient with a particularly high density of tau+ neurons in the hippocampus appeared to be atypical of the patient group studied. The data support the hypothesis that, although clinically heterogeneous, CBD is a pathologically distinct disorder. (C) 2000 Academic Press.

Lobe growth variation and the maintenance of symmetry in foliose lichen thalli

The aim of this study was to determine how thallus symmetry could be maintained in foliose lichens when variation in the growth of individual lobes may be high. Hence, the radial growth of a sample of lobes was studied monthly, over 22 months, in 7 thalli of Parmelia conspersa (Ehrh. Ex Ach.) Ach. And 5 thalli of P. glabratula ssp fuliginosa (fr. ex Duby) Laund. The degree of variation in the total radial growth of different lobes within a thallus over 22 months varied between thalli. Individual lobes showed a fluctuating pattern of radial growth from month to month with alternating periods of fast and slow growth. Monthly variations in radial growth of different lobes were synchronized in some but not in all thalli. Few significant correlations were found between the radial growth of individual lobes and total monthly rainfall or shortwave radiation. The levels of ribitol, arabitol and mannitol were measured in individual lobes. All three polyols varied significantly between lobes within a thallus suggesting that variations in algal phostosynthesis and in the partitioning of fungal polyols may contribute to lobe growth variation. The effect on thallus symmetry of lobes which grew radially either consistently faster or slower than average was studied. Slow growing lobes were overgrown, and gaps in the perimeter were eliminated by the growth of neighbouring lobes, in approximately 7 to 9 months. However, a rapidly growing lobe, with its neighbours removed on either side, continued to grow radially at the same rate as rapidly growing control lobes. The results suggested that lobe growth variation results from a combination of factors which may include the origin of the lobes, lobe morphology and the patterns of algal cell division and hyphal elongation in different lobes. No convincing evidence was found to suggest that exchange of carbohydrate occurred between lobes which would tend to equalize their radial growth. Hence, the fluctuating pattern of lobe growth observed may be sufficient to maintain a degree of symmetry in most thalli. In addition, slow growing lobes would tend to be overgrown by faster growing neighbours thus preventing the formation of indentations in the thallus perimeter.

Nonlinearity in all-night sleep EEG recorded with foramen ovale electrodes in a patient with temporal lobe epilepsy

Objective: It is investigated to which extent measures of nonlinearity derived from surrogate data analysis are capable to quantify the changes of epileptic activity related to varying vigilance levels. Methods: Surface and intracranial EEG from foramen ovale (FO-)electrodes was recorded from a patient with temporal lobe epilepsy under presurgical evaluation over one night. Different measures of nonlinearity were estimated for non-overlapping 30-s segments for selected channels from surface and intracranial EEG. Additionally spectral measures were calculated. Sleep stages were scored according to Rechtschaffen/Kales and epileptic transients were counted and classified by visual inspection. Results: In the intracranial recordings stronger nonlinearity was found ipsilateral to the epileptogenic focus, more pronounced in NREM sleep, weaker in REM sleep. The dynamics within the NREM episodes varied with the different nonlinearity measures. Some nonlinearity measures showed variations with the sleep cycle also in the intracranial recordings contralateral to the epileptic focus and in the surface EEG. It is shown that the nonlinearity is correlated with short-term fluctuations of the delta power. The higher frequency of occurrence of clinical relevant epileptic spikes in the first NREM episode was not clearly reflected in the nonlinearity measures. Conclusions: It was confirmed that epileptic activity renders the EEG nonlinear. However, it was shown that the sleep dynamics itself also effects the nonlinearity measures. Therefore, at the present stage it is not possible to establish a unique connection between the studied nonlinearity measures and specific types of epileptic activity in sleep EEG recordings.

Spatial patterns of the pathological changes in neuronal intermediate filament inclusion disease (NIFID):an α-internexin immunohistochemical study

Neuronal intermediate filament inclusion disease (NIFID) is characterized by α-internexin positive neuronal cytoplasmic inclusions (NCI), swollen achromatic neurons (SN), neuronal loss, and gliosis. This study tested: 1) whether the spatial patterns of the lesions was topographically organized in areas of the frontal and temporal lobe and 2) whether a spatial relationship exists between the NCI and SN. The NCI were distributed in regular clusters and in a quarter of these areas, the clusters were 400-800 μm in diameter approximating to the size of the cells of origin of the cortico-cortical pathways. Variations in the density of the NCI were positively correlated with the SN. Hence, cortical degeneration in NIFID appears to be topographically organized and may affect the cortico-cortical projections, the clusters of NCI and SN developing within the same vertical columns of cells. © 2007 Springer-Verlag.

Topography of α-internexin-positive neuronal aggregates in 10 patients with neuronal intermediate filament inclusion disease

Abnormal neuronal intermediate filament (IF) inclusions immunopositive for the type IV IF α-internexin have been identified as the pathological hallmark of neuronal intermediate filament inclusion disease (NIFID). We studied the topography of these inclusions in the frontal and temporal lobe in 68 areas from 10 cases of NIFID. In the cerebral cortex, CA sectors of the hippocampus, and dentate gyrus granule cell layer, the inclusions were distributed mainly in regularly distributed clusters, 50-800 μm in diameter. In seven cortical areas, there was a more complex pattern in which the clusters of inclusions were aggregated into larger superclusters. In 11 cortical areas, the size of the clusters approximated to those of the cells of origin of the cortico-cortical pathways but in the majority of the remaining areas, cluster size was smaller than 400 μm. The topography of the lesions suggests that there is degeneration of the cortico-cortical projections in NIFID with the formation of α-internexin-positive aggregates within vertical columns of cells. Initially, only a subset of cells within a vertical column develops inclusions but as the disease progresses, the whole of the column becomes affected. The corticostriate projection appears to have little effect on the cortical topography of the inclusions. © 2006 EFNS.

Spatial patterns of the pathological changes in the temporal lobe of patients with neuronal intermediate filament inclusion disease

Neuronal intermediate filament inclusion disease (NIFID) is a new neurodegenerative disease characterized histologically by the presence of neuronal cytoplasmic inclusions (NI) immunopositive for intermediate filament proteins, neuronal loss, swollen achromatic neurons (SN), and gliosis. We studied the spatial patterns of these pathological changes parallel to the pia mater in gyri of the temporal lobe in four cases of NIFID. Both the NI and SN occurred in clusters that were regularly distributed parallel to the pia mater, the cluster sizes of the SN being significantly greater than those of the NI. In a significant proportion of areas studied, there was a spatial correlation between the clusters of NI and those of the SN and with the density of the surviving neurons. In addition, the clusters of surviving neurons were negatively correlated (out of phase) with the clusters of glial cell nuclei. The pattern of clustering of these histological features suggests that there is degeneration of the cortico-cortical projections in NIFID leading to the formation of NI and SN within the same vertical columns of cells. The glial cell reaction may be a response to the loss of neurons rather than to the appearance of the NI or SN.

Quantification of the pathological changes in the temporal lobe of patients with a novel neurofilamentopathy: neurofilament inclusion disease (NID)

Objective: To quantify the densities of neurofilament inclusions (NI), swollen achromatic neurons, surviving neurons and glial cells in a novel neurofilamentopathy neurofilament inclusion disease (NID). Material: Sectionsof temporal lobe from 4 cases of NID stained with an antibody raised to neurofilament proteins. Method: Densities of the pathological changes were estimated in the various gyri of the temporal lobe, hippocampus and dentate gyrus. Results: Densities of the NI and swollen achromatic neurons (SN) were greater in the cerebral cortical gyri than in the hippocampus and dentate gyrus. Lesion density was relatively constant between gyri and between the CA sectors of the hippocampus. In cortical gyri, the density of the NI, SN and glial cell nuclei was greater in laminae II/III than laminae V/VI. Densities of the NI were negatively correlated with the surviving neurons and positively correlated with the glial cell nuclei. The density of the SN was positively correlated with that of the surviving neurons. Conclusion: The pathology of NID morphologically resembles that of Pick's disease (PD) and corticobasal degeneration (CBD), but there are distinct differences between NID and these disorders supporting the hypothesis that NID is a novel and unique type of neurodegenerative disease.

Temporal lobe pathology of human patients with neurofilament inclusion disease

Neurofilament inclusion disease (NID) is a novel neurodegenerative disease characterized histologically by the presence of neurofilament positive neuronal inclusions (NI) and swollen achromatic neurons (SN). The density and distribution of NI and SN were studied in areas of the temporal lobe in four cases of NID. In NID, the density of the NI and SN was greater in areas of the cerebral cortex compared with the hippocampus and dentate gyrus. Lesion densities were similar in the different gyri of the temporal cortex and in the various cornu ammonis sectors of the hippocampus. In the cerebral cortex, the density of the NI and SN was greater in the lower compared with the upper cortical laminae. There was no significant correlation between the densities of the NI and SN. The distribution of the temporal lobe pathology of NID has several differences from that reported in Pick's disease and corticobasal degeneration supporting the hypothesis that NID is a novel and unique type of neurodegenerative disease. © 2003 Elsevier Ireland Ltd. All rights reserved.

Lobe connections and lobe crowding are associated with growth rate in the lichen Xanthoparmelia conspersa

The association between lobe connections and the degree of lobe crowding and radial growth was studied in thalli of the foliose lichen Xanthoparmelia conspersa. In 35 thalli, 15% of the lobes were not physically connected to either of their neighbours before the lobes merged into the centre of the thallus. Twenty-five percent of the lobes were connected in pairs and 29% in groups of three. Approximately 5% of the lobes were interconnected in larger groups of six or more. The mean number of lobes per group in a thallus was positively correlated with thallus diameter and with the degree of lobe growth variation but was unrelated to annual radial growth rate (RGR). The degree of crowding of the lobes in a thallus was defined as a 'crowding index', viz., the product of lobe density and mean lobe width. Crowding index increased rapidly with size in smaller thalli but changed less with size in larger thalli. Crowding index was positively correlated with RGR but was unrelated to lobe growth variation. Lobes removed from large thalli and glued in various configurations to simulate different degrees of crowding did not demonstrate an association between lobe crowding and RGR over one year. These results suggest that the pattern of lobe connectivity of a thallus is associated with lobe growth variation in X. conspersa. The degree of lobe crowding is associated with the increase in RGR with thallus size in smaller thalli and by restricting lobe width, could also be a factor associated with the more constant growth of larger thalli.

Quantification of vacuolation ('spongiform change'), surviving neurones and prion protein deposition in eleven cases of variant Creutzfeldt-Jakob disease

Vacuolation ('spongiform change') and prion protein (PrP) deposition were quantified in the cerebral cortex, hippocampus, dentate gyrus and molecular layer of the cerebellum in 11 cases of variant Creutzfeldt-Jakob disease (vCJD). The density of vacuoles was greater in the cerebral cortex compared to the hippocampus, dentate gyrus and cerebellum. Within the cortex, vacuole density was significantly greater in the occipital compared to the temporal lobe and the density of surviving neurones was greatest in the occipital lobe. The density of the non-florid PrP plaques was greater in the cerebellum compared to the other brain areas. There were significantly more florid-type PrP plaques in the cerebral cortex compared to the hippocampus and the molecular layer of the cerebellum. No significant correlations were observed between the densities of the vacuoles and the PrP plaques. The densities of vacuoles in the parietal cortex and the non-florid plaques in the frontal cortex were positively correlated with the density of surviving neurones. The densities of the florid and the non-florid plaques were positively correlated in the parietal cortex, occipital cortex, inferior temporal gyrus and dentate gyrus. The data suggest: (i) vacuolation throughout the cerebral cortex, especially in the occipital lobe, but less evident in the hippocampus and molecular layer of the cerebellum; (ii) the non-florid plaques are more common than the florid plaques and predominate in the molecular layer of the cerebellum; and (iii) either the florid plaques develop from the non-florid plaques or both types are morphological variants resulting from the same degenerative process.

Experimental studies of lobe growth in the lichen Parmelia conspersa (Ehrh. Ex Ach.) Ach.

The radial growth of individual lobes of the foliose lichen, Parmelia conspersa (Ehrh. Ex Ach.) Ach. was studied to determine whether (1) adjacent lobes exchange carbohydrate and (2) marginal competition between lobes influences radial growth. In a survey of thalli of different size, the number of marginal lobes was linearly related to thallus circumference. However, the relationship between mean lobe width and thallus circumference was fitted by a second order polynomial. Hence, mean lobe width may reach a maximum in thalli approx. 3 cm in diameter. The interactions between marginal lobes were studied by either painting single lobes with acrylic paint or by removing lobes from the thallus. Painting the whole lobe virtually stopped its radial growth while partially painted lobes grew less than control lobes. The radial growth of a lobe was unaffected by either completely painting or removing its neighbour. Removal of both neighbouring lobes did not influence the radial growth of a lobe but severing the lobe from the thallus reduced its radial growth. In addition, lobe width increased significantly when both neighbouring lobes were removed. These results suggest that adjacent lobes have a considerable degree of independence and that there is little exchange of carbohydrate between them. In addition, marginal competition between adjacent lobes may restrict the lateral extension of the lobe and this may maintain a more constant mean lobe width in larger thalli. It is possible that the intensity of marginal competition between adjacent lobes may vary with thallus size and this could be a factor determining the growth curve of a foliose lichen throughout its life.

Lobe growth in foliose lichen thalli

The margins of foliose lichen thalli comprise individual lobes which grow radially and divide. This results in a complex marginal structure in which lobes differing in morphology, state of division, and growth pattern are crowded together. Various aspects of the biology of these lobes are reviewed including their carbohydrate supply, morphology, pattern of division and branching, the effect of lobe overcrowding and interactions between neighbouring lobes. As the thalus grows, lobes become increasingly crowded together and this restricts further lateral growth. Restriction of lobe width may be reponsible for the changes in radial growth rate (RGR) with size observed in foliose species. Various aspects of lobe biology may be responsible for lobe growth variation including the physical independence of lobes from their neighbours, the genetic origin of the lobes, and the pattern of lobe branching. Overall symmetry of a thallus is maintained by a fluctuating pattern of growth of individual lobes in successive months together with competition for space at the margin