1/90. Familial frontotemporal dementia with ubiquitin-positive, tau-negative inclusions.OBJECTIVE: To describe the clinical features, neuropathology, and genetic studies in a family with autosomal dominant frontotemporal dementia (FTD). BACKGROUND: Clinical Pick's disease, or FTD with parkinsonism, has been described in several families linked to chromosome 17 (FTDP-17). Most of these have shown tau protein mutations. The clinical and pathologic variations in these families resemble the spectrum of sporadic FTD or "Pick complex." methods: Clinical and behavioral analysis of the affected members with extensive histochemical and neuropathologic description of three cases, genetic analysis of three clinically affected members and seven at risk members to assess linkage to chromosome 17, and sequencing of the tau gene in two patients were performed. RESULTS: The clinical pattern shows a highly stereotypic disinhibition dementia with late extrapyramidal features, progressive mutism, and terminal dysphagia in three generations of affected individuals. Neuropathology showed frontotemporal atrophy, and microscopically tau- and synuclein-negative and ubiquitin-positive neuronal inclusions, in the background of superficial cortical spongiosis, neuronal loss, and gliosis. Tau expression was restricted to oligodendroglia. All exons and surrounding introns of the tau gene were sequenced, and no mutation or disease-related polymorphisms were detected in either of two affected pedigree members. CONCLUSION: This family with autosomal dominant frontotemporal dementia (FTD) shows no tau expression in neurons. The ubiquitin-positive, tau-negative inclusions have been described before in FTD with and without motor neuron disease, but not in a familial form. The clinical and some pathologic features are similar to those of several of the families included in descriptions of FTD with parkinsonism linked to chromosome 17, but the linkage to tau has been excluded. The defect in this family, however, could be functionally related to tau mutations.- - - - - - - - - - ranking = 1keywords = gliosis (Clic here for more details about this article) |
2/90. dna damage and activated caspase-3 expression in neurons and astrocytes: evidence for apoptosis in frontotemporal dementia.frontotemporal dementia (FTD) is a neurodegenerative disease which affects mainly the frontal and anterior temporal cortex. It is associated with neuronal loss, gliosis, and microvacuolation of lamina I to III in these brain regions. In previous studies we have described neurons with dna damage in the absence of tangle formation and suggested this may result in tangle-independent mechanisms of neurodegeneration in the AD brain. In the present study, we sought to examine dna fragmentation and activated caspase-3 expression in FTD brain where tangle formation is largely absent. The results demonstrate that numerous nuclei were TdT positive in all FTD brains examined. Activated caspase-3 immunoreactivity was detected in both neurons and astrocytes and was elevated in FTD cases as compared to control cases. A subset of activated caspase-3-positive cells were also TdT positive. In addition, the cell bodies of a subset of astrocytes showed enlarged, irregular shapes, and vacuolation and their processes appeared fragmented. These degenerating astrocytes were positive for activated caspase-3 and colocalized with robust TdT-labeled nuclei. These findings suggest that a subset of astrocytes exhibit degeneration and that dna damage and activated caspase-3 may contribute to neuronal cell death and astrocyte degeneration in the FTD brain. Our results suggest that apoptosis may be a mechanism of neuronal cell death in FTD as well as in AD (228).- - - - - - - - - - ranking = 1keywords = gliosis (Clic here for more details about this article) |
3/90. Familial frontotemporal dementia with a P301L tau mutation in japan.We have reported the family line with frontotemporal dementia (FTD) in japan. This family line has so far included four patients. Patient II-1 (man) had a 10 year history of slowly progressive personality and behavioral changes and died at the age of 56. His neuropathological examination showed severe atrophy of the bilateral frontal and temporal cortices with neuronal loss, gliosis and superficial spongiosis. Pick bodies were not found. The neuropathological diagnosis was atypical Pick's disease without Pick bodies or Pick-type in FTD. Patient III-2 is patient II-1's oldest daughter and was taken ill with personality change at the age of 52. She died at the age of 68. Patient III-4 is patient II-1's second daughter. Her onset with strange speech and behavior was at the age of 59. Patient III-5 is patient II-1's oldest son. He also had onset with personality change at the age of 54 and had the P301L mutation in tau. In all III generation cases CT/MRI revealed circumscribed frontotemporal atrophy. Patient III-5's PET/SPECT showed signs of hypoperfusion or hypometabolism in the bilateral frontotemporal areas. This is the first report of familial FTD with the P301L mutation in japan.- - - - - - - - - - ranking = 1keywords = gliosis (Clic here for more details about this article) |
4/90. A new case of frontotemporal dementia and parkinsonism resulting from an intron 10 3-splice site mutation in the tau gene: clinical and pathological features.Hereditary frontotemporal dementia and parkinsonism (FTDP) linked to chromosome 17 (FTDP-17) constitutes a new form of tauopathy, and mutations in the tau gene have recently been reported in some affected families. This report presents clinical and neuropathological data from a member of a British family (SOT 254) with a history of dementia and movement disorder. The medical history of the affected patient, a woman aged 44 years, was reviewed, and a detailed post-mortem examination of the brain was undertaken. A panel of well characterized phosphorylation-dependent and independent anti-tau antibodies was used to assess tau pathology, and inclusions were examined by electron microscopy. Neuronal loss and gliosis were widely distributed, but most severe in neocortical regions, and were associated with abundant neuronal and glial tau inclusions which consisted of a mixture of paired helical filaments (PHFs), similar to those in Alzheimer's disease, and distinct twisted ribbon-like filaments. Genomic DNA was obtained from post-mortem tissue from the index patient, and blood from two unaffected members of the same family. For the index case only, sequencing of intronic sequences flanking exon 10 of the tau gene identified a G to A transition at position 3 of the splice-donor site downstream of exon 10, identical to that reported in multiple system tauopathy with presenile dementia (MSTD). The clinical, neuropathological and genetic findings strongly suggest that SOT 254 represents a new example of FTDP-17 resulting from a mutation in the tau gene. These results are compared with those reported for other FTDP-17 families, i.e. for MSTD.- - - - - - - - - - ranking = 1keywords = gliosis (Clic here for more details about this article) |
5/90. A new familial adult-onset leukodystrophy manifesting as cerebellar ataxia and dementia.BACKGROUND: Among hereditary leukodystrophies, a considerable number remain unclassified. patients AND RESULTS: We investigated the clinical course and histopathology of one patient in a family of adult-onset leukodystrophy with possible dominant inheritance. A 44-year-old man presented with cerebellar ataxia as the initial symptom, and later, dementia and hyperreflexia with ankle clonus developed. T2-weighted brain MRI showed brain atrophy and diffuse high signal intensity of the cerebral white matter and the brain stem. The patient's mother and older brother also had cerebellar ataxia and dementia, and his older brother had been diagnosed as having spinocerebellar degeneration. An older sister of our patient possibly had similar neurological symptoms of adult-onset. Our patient died of pneumonia 5 years after the onset of disease. The histopathological findings consisted mainly of patchily observed vacuolar changes in the cerebral and cerebellar white matter and the brain stem. The subcortical regions and the cortex were unaffected. It is suggested that the pathological changes began in the cerebellum, and later spread to the frontal lobe and the brain stem. In the occipital regions, the vacuolations were associated with accumulation of macrophages and astrocytosis, which implied that the vacuolations were of recent origin. CONCLUSIONS: The diagnosis in this patient is adult-onset leukodystrophy with possibly autosomal dominant inheritance. The clinicopathological features are different from those, of previously reported adult-onset leukodystrophies.- - - - - - - - - - ranking = 5.8705580300573keywords = astrocytosis (Clic here for more details about this article) |
6/90. frontal lobe dementia with novel tauopathy: sporadic multiple system tauopathy with dementia.We present a novel tauopathy in a patient with a 10-yr history of progressive frontal lobe dementia and a negative family history. autopsy revealed mild atrophy of frontal and parietal lobes and severe atrophy of the temporal lobes. There were occasional filamentous tau-positive inclusions, but more interesting were numerous distinctive globular neuronal and glial tau-positive inclusions in both gray and white matter of the neocortex. Affected subcortical regions included substantia nigra, globus pallidus, subthalamic nucleus, and cerebellar dentate nucleus, in a distribution similar to progressive supranuclear palsy (PSP), but without significant accompanying neuronal loss or gliosis. Predominantly straight filaments were detected by electron microscopy (EM), while other inclusions were similar to fingerprint bodies. No twisted ribbons were detected. Immuno-EM studies revealed that only the filamentous inclusions were composed of tau. immunoblotting of sarkosyl-insoluble tau revealed 2 major bands of 64 and 68 kDa. Blotting analysis after dephosphorylation revealed predominantly 4-repeat tau. sequence analysis of tau revealed that there were no mutations in either exons 9-13 or the adjacent intronic sequences. The unique cortical tau pathology in this case of sporadic multiple system tauopathy with dementia adds a new pathologic profile to the spectrum of tauopathies.- - - - - - - - - - ranking = 1keywords = gliosis (Clic here for more details about this article) |
7/90. Creutzfeldt-Jakob disease (CJD) in a case of suspected chronic heavy metal poisoning.We describe a patient who died of suspected heavy metal poisoning after a nine-month history of rapidly worsening dementia. autopsy at a forensic-pathological institute established the postmortem diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) based on demonstration of the proteinase-resistant prion protein (PrPsSc) in Western-Blot on native brain tissue. Microscopic examination of the macroscopically largely inconspicuous brain revealed marked spongiform changes in the gray matter--mainly affecting the cerebral cortex, nucleus caudatus, and putamen--with confluent vacuoles. Patchy or perivacuolar deposits of PrPSc were found as well as granular PrPsc deposits. The cerebellum contained focal PrPsc deposits. There was an astrogliosis in the white matter and a proliferation of microglia in the gray matter with a simultaneous clear reduction in neuronal elements. The differential diagnosis is discussed, as is the potential risk to those performing autopsy on forensic cases with a clinical picture of rapidly progressing dementia, especially in cases where a prion disease is not initially suspected.- - - - - - - - - - ranking = 1keywords = gliosis (Clic here for more details about this article) |
8/90. Late-onset neurodegeneration with brain iron accumulation type 1: expanding the clinical spectrum.We report on two patients with pathologically proven neurodegeneration with brain iron accumulation type 1 (NBIA-1) with late onset and atypical presentations. One patient experienced gradual onset of shuffling gait, rigidity, bradykinesia, and increasing postural instability at age 85 years. He died a few weeks after developing acute hemiballismus at age 90 years. Histopathology revealed marked neuronal loss in the internal segment of the globus pallidum, astrocytosis, axonal spheroids, and extensive iron deposition consistent with NBIA-1. No additional lesions were found to explain the hemiballismus. The second patient experienced fulminant dementia evolving to total disability and death within 2 months. autopsy showed typical NBIA-1 pathology. We conclude that NBIA-1 pathology can develop at any age, and that the phenotype should be expanded to include late-onset parkinsonism. The relationship to hemiballismus and adult-onset dementia is less clear.- - - - - - - - - - ranking = 5.8705580300573keywords = astrocytosis (Clic here for more details about this article) |
9/90. The use of antioxidants in transmissible spongiform encephalopathies: a case report.BACKGROUND: Transmissible spongiform encephalopathies (TSE), which include Creutzfeldt-Jakob disease and new variant Creutzfeldt-Jakob disease, are diseases characterized by progressive deterioration in the central nervous system with neuronal degeneration, vacuolatization of the neuropil, and gliosis. Little is known about the pathogenic mechanisms of infection, and controversy exits around the inciting infective agent. It has been shown that an important factor in pathogenesis is the immune system. CASE: The reported case points to beneficial effects when antioxidant therapies are used in transmissible spongiform encephalopathies. The case revealed an early reversal in cognitive decline and subsequent improvements in myoclonus, apnea and rigidity. Although death was the ultimate outcome, the patient succumbed to the illness over 22 months after the onset of symptoms when the early rapid decline predicted demise within a few months. CONCLUSION: It is possible that strategies blocking the effect of proinflammatory cytokines and the resulting oxidative damage may stem the progressive damage to the neuropil that occurs in spongiform encephalopathies. Further investigation into the use of antioxidants and other types of agents quelling inflammation needs to be undertaken. If antioxidants could be combined with treatments for the inciting infective agent, a new direction could be taken in the outcome of transmissible spongiform encephalopathies including CJD and vCJD.- - - - - - - - - - ranking = 1keywords = gliosis (Clic here for more details about this article) |
10/90. frontotemporal dementia: a clinical-pathological study.We report a 44-year-old female patient without any familial history of dementia presenting with increasing disturbances in behaviour and language followed by a progressive cognitive deterioration. Neuropsychological evaluation revealed a significant impairment on frontal lobe tests. A brain PET scan disclosed a severe frontal hypometabolism. The tentative diagnosis of frontotemporal dementia was made. Her condition rapidly worsened and she died 2 years after the beginning of her disease. Gross examination of the brain showed a selective symmetrical atrophy of both frontal and anterior part of the temporal lobes. Microscopical examination revealed severe neuronal loss in the frontal and anterior temporal cortex associated with gliosis and microvascular spongiosis in the superficial cortical layers in the absence of any specific neuronal or glial inclusions. These neuropathological findings were consistent with the diagnosis of dementia lacking distinctive histology. We discuss the nosology of the frontotemporal dementias, the diagnostic value of PET scan, the recent genetical developments which strongly support the pathogenic role of tau and we emphasize the importance of immunohistochemical examination for a definite neuropathological diagnosis.- - - - - - - - - - ranking = 1keywords = gliosis (Clic here for more details about this article) |
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