Showing papers by "Herbert Budka published in 1997"

Alterations in glia and axons in the brains of Binswanger's disease patients.

Abstract: Background and Purpose Although increasing attention is being paid to Binswanger’s disease, a form of vascular dementia characterized by diffuse white matter lesions, only limited information is available on the pathological changes that occur in the glia and axons in the white matter. We therefore investigated the brains of patients with Binswanger’s disease to gain further insight into its pathophysiology. Methods Autopsied brains from patients with Binswanger’s disease (group 3; n=17) were compared with those of non-neurological controls (group 1; n=5) and controls with large cortical infarcts but without significant white matter lesions (group 2; n=5). Glial fibrillary acidic protein (GFAP) was used as an immunohistochemical marker for astroglia, leukocyte common antigen (LCA) was used as a marker for microglia, and HLA-DR was used as a marker for activated microglia. Axonal damage was assessed by the accumulation of proteins, which are transported by fast axonal flow, amyloid protein precursor (APP), synaptophysin, and chromogranin A. Results Although there was no difference in numerical density of GFAP-immunoreactive astroglia in each group, regressive astroglia were observed in 7 of 17 patients with Binswanger’s disease. LCA-immunoreactive microglia were 1.7 times more numerous in Binswanger’s disease than in group 1 ( P P P Conclusions The pathological alterations in Binswanger’s diseased brains include regressive changes in the astroglia and activation of the microglia with a decrease in the oligodendroglia, which were associated with the degradation of both myelin and axonal components. These results indicate that an inflammatory reaction and compromised axonal transport, mediated by chronic ischemia, may play an important role in the pathophysiology of Binswanger’s disease.

Distribution of parvalbumin-immunoreactive neurons in brain correlates with hippocampal and temporal cortical pathology in Creutzfeldt-Jakob disease

Abstract: There is a distinctive pattern of hippocampal involvement in Creutzfeldt-Jakob disease (CJD) and evidence for selective vulnerability of GABAergic neurons in experimental and human prion disease. We studied hippocampus and temporal cortex from human CJD and control autopsy brains and surgical cryptogenic temporal lobe epilepsy specimens for distribution and density of parvalbumin (PV) and calbindin-D28K (Cal) -positive neurons that are subpopulations of GABAergic neurons. Pathology was evaluated semiquantitatively in 8 regions in 23 CJD brains for severity of spongiform change, astrogliosis and pathological prion protein deposition. In CJD, pathology was severe in pre-parasubiculum and temporal cortex, and little or absent in CA1-4; PV+ neurons were severely reduced or absent in all cases, whereas Cal+ neurons were largely preserved. In controls, the density of PV+ neurons was highest in pre-parasubiculum and temporal cortex, and lowest in CA1-4. In cTLE, loss of PV+ neurons was seen only in CA1-4. The diffuse and severe loss of PV+ neurons in CJD, and the topographical correlation of tissue lesioning in CJD with density of PV+ neurons in controls suggest selective vulnerability and early loss of this subset of inhibitory neurons in CJD. This might relate to characteristic CJD symptoms such as myoclonus and the distinctive EEG pattern.

Pathology and Immunocytochemistry of a Kuru Brain

Abstract: We report here results of modern staining techniques including anti-prion protein (PrP) immunocytochemistry to a set of archival brain specimens of a 16 year-old male who died from kuru in 1967. Brain suspensions transmitted disease to chimpanzees and New World monkeys. The PrP gene is homozygous for valine at the polymorphic codon 129. Histology shows neuronal loss, spongiform change, and astrogliosis. Lesions are maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, striatum, and thalamus, and are accentuated in middle and deep cerebral cortical layers. PrP accumulates as diffuse synaptic type deposits and mostly unicentric plaques. PrP deposition is maximal in parasagittal and interhemispheric areas of frontal, central and parietal cortex, cingulate cortex, basal ganglia, and cerebellar cortex. Plaques are prominent in the striatum, thalamus, and granular layer of cerebellar cortex. Meticulous examination reveals only rare “florid” plaques with surrounding vacuolation. We conclude that 1) pathology including immunomorphology of PrP deposition in this kuru brain is within the lesion spectrum of Creutzfeldt-Jakob disease although plaques are unusually prominent and widespread; 2) kuru does not share the neuropathological hallmarks of the new Creutzfeldt-Jakob disease variant recently reported in the UK and France; 3) topographic prominence of PrP deposition parallels that of spongiform change and/or astrogliosis.

Ganglionitis in paraneoplastic subacute sensory neuronopathy: a morphologic study.

Abstract: A 69-year-old woman presented with subacute sensory neuropathy and autonomic dysfunction of 9 months' duration, associated with high serum titers of anti-Hu antibodies. A small cell carcinoma of the lung was diagnosed by biopsy. She died after cardiorespiratory arrest. At autopsy, spinal and autonomic ganglia showed subacute inflammation with diffuse endoneurial T-cell, B-cell, and plasma cell infiltration. The cytoplasm and nuclei of some ganglion neurons displayed IgG immunocytochemical positivity. CD8+ T cells were tightly attached to, and indented the cell surface of, IgG-positive and IgG-negative neurons. This observation suggests that both cytotoxic T-cell-mediated attack against neurons and humoral mechanisms play a role in paraneoplastic subacute sensory neuronopathy.

Central nervous system pathology in patients with the Guillain-Barré syndrome.

Abstract: Thirteen autopsy cases of patients with clinical criteria of the Guillain-Barre syndrome were investigated for pathological changes and cellular composition of inflammatory infiltrates in the CNS and PNS. The survival times from the onset of neurological symptoms until death ranged from 1 day to 12 months. In the CNS, degeneration of spinal posterior tracts was seen in three cases. Mononuclear infiltrates consisted of evenly proportioned lymphocytes and macrophages in cases with survival of 1 and 2 days, whereas macrophages predominated in cases with survival of 5 days and longer. Infiltrates presented as nodular clusters around blood vessels and neurons, or were scattered diffusely. They were found within the spinal cord in eight out of 13 cases, within the medulla oblongata in eight out of 12 cases, within the pons in five out of nine cases, and in one out of four midbrains. Activation of microglia, either focal or diffuse, was found in various degrees in 11 out of 13 cases, involving the spinal cord (six out of 13 cases), the medulla oblongata (10 out of 12 cases), the pons (five out of nine cases) or as subependymal rims along the walls of the ventricular system and the central canal of the spinal cord (seven out of 13 cases). In the PNS, myelin loss (12 out of 13 cases), axonal degeneration (six out of 13 cases) and mononuclear cell infiltrates (13 out of 13 cases) were seen in segmental and cranial nerves, spinal ganglia and spinal roots in varying distribution and severity. Mononuclear cell infiltrates were composed of macrophages and T lymphocytes, with even distribution in cases with short survival (1 and 2 days), and predominance of macrophages in cases with protracted clinical course. T lymphocytes were equally composed of OPD4+ and CD8+ cells without obvious differences between cases of short and long duration, or between PNS and CNS infiltrates in 11 out of 12 cases, whilst two cases had a dominant OPD4+ subset. We conclude that CNS pathology is frequent in patients with Guillain-Barre syndrome. It involves axons with secondary myelin impairment, microglial activation and inflammatory infiltration. In this series, primary demyelination is not found in the CNS. Changes such as degeneration of spinal posterior tracts are secondary to pathology in the PNS. Inflammatory cell reactions in the CNS are similar to those in the PNS and to CNS pathology in experimental allergic neuritis. This inflammation might reflect CNS immune activation in the absence of the relevant antigen, in addition to cellular reactions accompanying secondary CNS changes. The presence of distinct pathology in the CNS is in contrast with other recent studies on the pathology of Guillain-Barre syndrome which, unlike this study, may have been influenced by recently introduced treatments.

Proliferation and DNA fragmentation in meningioma subtypes

Abstract: H Maier, J Wanschitz, R Sedivy, K Rossler, D Ofner and H Budka (1997) Neuropathology and Applied Neurobiology23, 496–506 Proliferation and DNA fragmentation in meningioma subtypes Atypical meningioma has been introduced as tumour subtype of intermediate biological behaviour between classical and malignant meningiomas To substantiate this three-step scale of malignancy, we assessed the proliferative activity reflected by Ki-67 (MIB1) labelling index (LI) in a series of 89 meningiomas, including 15 classical, 29 atypical, 35 anaplastic tumours, and 10 haemangiopericytomas and papillary meningiomas The possible correlation of proliferation with the frequency of apoptosis and their relations to BCL-2 immunoexpression was investigated in seven classical, 10 atypical and 10 malignant meningiomas Apoptosis was demonstrated by evaluation of the frequency of apoptotic figures, by the enzymatic technique of in situ tailing (IST) which stains apoptotic DNA fragments, and by DNA preparation and gel electrophoresis demonstrating DNA laddering in frozen tissues of five meningiomas MIB1 LI revealed a highly significant increase from classical through atypical to anaplastic meningiomas (P 00001); haemangiopericytomas and papillary meningiomas were well within the range of atypical meningiomas IST indices rose with increasing malignancy and correlated with MIB1 LI (P 00001); they showed a weak inverse correlation with BCL-2 immunoexpression (P= 005) BCL-2 expression tended to decrease with malignancy grade and was unrelated to MIB1 LI or frequency of apoptosis Our data show that (i) apoptosis is a feature of meningiomas, significantly correlated with the malignancy scale, (ii) DNA fragmentation shows significant correlation with proliferation and inversely with BCL-2 expression; (iii) proliferation indices and frequencies of apoptosis/DNA fragmentation within meningioma subgroups corroborate the intermediate biological position of the atypical meningioma between classical and malignant meningiomas

Naturally Occurring Herpes Simplex Encephalitis in a Domestic Rabbit (Oryctolagus cuniculus)

Abstract: An approximately 1-year-old domestic rabbit showed severe neurologic signs with circling and turning somersaults. Histologically, a nonsuppurative meningoencephalitis with neuronal cell necrosis and numerous intranuclear inclusion bodies in neurons and glial cells was found. Electron microscopic examination revealed herpesvirus particles in affected cells. A human herpes simplex virus was identified by means of immunocytochemistry and in situ hybridization as the causal agent and was further classified as herpes simplex virus 1 by polymerase chain reaction analysis. Because encephalitis is easily induced in rabbits by experimental infection with herpes simplex virus, the source of infection is suspected to be a human with herpes labialis who had close contact with the rabbit.

Absence of measles virus receptor (CD46) in lesions of subacute sclerosing panencephalitis brains

Abstract: In this study we investigated pathological changes of the expression of the measles virus (MV) receptor, CD46, in subacute sclerosing panencephalitis (SSPE) brains. We analyzed CD46 expression in lesions of brain specimens from five SSPE patients in comparison to uninfected regions of the same brains and to normal human brains. The correlation between CD46 and MV infection, in individual cells in SSPE brains, was analyzed by double-staining procedures using monoclonal antibodies (mAbs) and in situ hybridization to detect MV-specific mRNAs. We found that CD46 was expressed at relatively low levels by neurons and astrocytes in normal brains in comparison to neuroblastoma and astrocytoma cell lines. Within heavily infected (MV-positive) brain lesions of all five SSPE cases, CD46 was either not detected or was expressed to a lesser degree by neural cells, irrespective of whether MV antigens were detectable or not. In contrast, normal levels of CD46 were found in SSPE brain tissue distant from the lesion. Using in situ hybridization, mRNAs of both MV nucleocapsid and MV hemagglutinin (MV-H) were detected in all SSPE lesions, while no or only small amounts of MV-H protein were detected. MV-infected neurons were never found to express CD46. Although a strict correlation between levels of the MV-H protein and the absence CD46 could not be seen, these findings suggest that the CD46 expression is reduced by the MV infection in lesions of SSPE brains.

Metallothionein overexpression in human brain tumours.

Abstract: Metallothioneins (MTs) are metal binding proteins overexpressed in various human neoplasms which are associated with resistance to cytotoxic drugs. A series of 156 archival human brain tumours were investigated immunohistochemically for expression of MTs; these included 10 low-grade gliomas, 44 high-grade gliomas, 98 meningeal tumours (19 classical, 30 atypical, 38 anaplastic meningiomas, and 11 haemangiopericytomas or papillary meningiomas), and 4 other tumours. Low-grade gliomas showed heterogeneous MT expression; 32 high-grade gliomas (72.7%) showed MT expression of more than 25% of tumour cells without statistically significant differences between first operations and recurrent tumours. In 2 glioblastomas, the presence of MT was confirmed by Western blotting. The extent of MT immunoexpression showed a statistically significant inverse relationship to the degree of p53 immunoreactivity. In meningiomas, a tendency to a higher percentage of MT-expressing cells was observed from classical over atypical to anaplastic meningiomas, but these differences were not statistically significant. In conclusion, MT expression is present in a significant portion of, especially malignant, brain tumours and might be involved in their poor response to antineoplastic drugs.

The human prion diseases: from neuropathology to pathobiology and molecular genetics Final report of an EU Concerted Action

Abstract: The human prion disease: from neuropathology to pathobiology and molecular genetics. Final report of an EU concerted action

Non-HTLV-I associated pleomorphic T-cell lymphoma of the brain mimicking post-vaccinal acute inflammatory demyelination

Abstract: Two weeks after vaccination against tick-borne encephalitis (TBE), a 57-year-old female suddenly developed mental confusion and hemiparesis of the left side. Cranial MRI demonstrated extensive bilateral lesions in the fronto-parietal white matter of both hemispheres, suggesting an acute inflammatory demyelinating disease following vaccination. Despite administration of high-dose corticosteroids, the patient died 3 weeks after onset of neurological symptoms. Autopsy revealed diffuse infiltrates of a primary cerebral pleomorphic T-cell lymphoma of medium and large cell type. PCR on brain tissue for HTLV-I and serology for anti-HTLV-I antibodies in CSF and serum were negative; immunocytochemistry on brain tissue did not detect EBV-related antigen. This is the first recorded observation of a diffusely infiltrating primary central nervous system T-cell lymphoma, clinically and radiologically mimicking a fatal acute inflammatory demyelinating complication after vaccination.

Primary Neuroendocrine (Merkel Cell) Carcinoma of the Anterior Skull Base

Abstract: A case of a primary neuroendocrine (Merkel cell) carcinoma arising in the anterior skull base involving the dura, both frontal lobes, and the paranasal sinuses is presented. The tumor was completely removed by an enlarged bifrontal transbasal approach. The neuropathological, immunohistological, and electron microscopical investigation revealed all characteristics of a Merkel cell carcinoma, normally presenting as a skin carcinoma of the head and neck. The history, treatment, neuropathology, and possible explanation for this rare manifestation are discussed.

Encephalitogenic peptide (EP) in human cerebrovascular white matter lesions.

Abstract: The expression of encephalitogenic peptide (EP), a 68-86 amino acid sequence of guinea pig myelin basic protein (MBP), was investigated in autopsied brains with focal cerebral damage or with diffuse white matter (WM) lesions. EP immunoreactive fibers were distributed in parallel with fibers immunoreactive for amyloid protein precursor (APP), an indicator of WM damages. EP was expressed in the periphery of cerebral infarctions and hematoma in the acute and subacute stages, but was also distributed in diffuse WM lesions due to heterogeneous causes. These data indicate that EP epitopes are exposed specifically in ongoing WM damages, and that the destruction of myelin occurs sporadically in diffuse WM lesions of varying intensity.