1/65. A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy.Recently intronic and exonic mutations in the Tau gene have been found to be associated with familial neurodegenerative syndromes characterized not only by a predominantly frontotemporal dementia but also by the presence of neurological signs consistent with the dysfunction of multiple subcortical neuronal circuitries. Among families, the symptomatology appears to vary in quality and severity in relation to the specific Tau gene mutation and often may include parkinsonism, supranuclear palsies, and/or myoclonus, in addition to dementia. We carried out molecular genetic and neuropathological studies on two patients from a French family presenting, early in their fifth decade, a cognitive impairment and supranuclear palsy followed by an akinetic rigid syndrome and dementia. The proband died severely demented 7 years after the onset of the symptoms; currently, his brother is still alive although his disease is progressing. In both patients, we found a Tau gene mutation in exon 10 at codon 279, resulting in an asparagine to lysine substitution (N279K). Neuropathologically, widespread neuronal and glial tau accumulation in the cortex, basal ganglia, brain stem nuclei as well as in the white matter were the hallmark of the disease. These deposits were shown by immunohistochemistry and immunoelectron microscopy, using a battery of antibodies to phosphorylation-dependent and phosphorylation-independent epitopes present in multiple tau regions. In the neocortex, tau-immunopositive glial cells were more numerous than immunopositive neurons; the deeper cortical layers as well as the white matter adjacent to the cortex contained the largest amount of immunolabeled glial cells. In contrast, some brain stem nuclei contained more neurons with tau deposits than immunolabeled glial cells. The correlation of clinical, neuropathological and molecular genetic findings emphasize the phenotypic heterogeneity of diseases caused by Tau gene mutations. Furthermore, to test the effect of the N279K mutation and compare it with the effect of the P301L exon 10 mutation on alternative splicing of Tau exon 10, we used an exon amplification assay. Our results suggest that the N279K mutation affects splicing similar to the intronic mutations, allowing exon 10 to be incorporated more frequently in the Tau transcript.- - - - - - - - - - ranking = 1keywords = neuron (Clic here for more details about this article) |
2/65. "Apraxia of eyelid opening" induced by levodopa therapy and apomorphine in atypical parkinsonism (possible progressive supranuclear palsy): a case report.We report a female patient in whom so-called apraxia of eyelid opening (AEO) developed after the onset of possible progressive supranuclear palsy (national institute of neurological disorders and stroke criteria) and the introduction of antiparkinsonian medications including levodopa. Although parkinsonian symptoms responded poorly to levodopa, AEO worsened after increasing levodopa dosage and disappeared when levodopa was discontinued. Later, a dose of apomorphine widely accepted for acute tests had no significant effect on limb motor activity but induced AEO. overall, these observations are grounds for thinking that AEO developing in the course of parkinsonism may be either disease- or drug-related. The possibility of manipulating dopaminergic treatment should always be considered when dealing with AEO associated with parkinsonism.- - - - - - - - - - ranking = 0.0058145679750962keywords = motor (Clic here for more details about this article) |
3/65. amyotrophic lateral sclerosis with supranuclear ophthalmoplegia and rigidity.ophthalmoplegia is rarely reported in patients with amyotrophic lateral sclerosis (ALS). We describe a patient with sporadic ALS, who had developed progressive external ophthalmoplegia of supranuclear origin and rigidity in the neck. autopsy findings showed histopathological abnormalities consistent with ALS. In addition to these findings, there was neuronal loss and gliosis in the putamina and globi pallidi, and gliosis in the periaqueductal gray matter. Our case appears to raise the possibility that ALS comprises a heterogenous group of disorders.- - - - - - - - - - ranking = 0.58815004482843keywords = neuron, lateral sclerosis, sclerosis (Clic here for more details about this article) |
4/65. Corticobasal degeneration: an autopsy case clinically diagnosed as progressive supranuclear palsy.We report an autopsy case diagnosed clinically as progressive supranuclear palsy (PSP), but neuropathologically confirmed as corticobasal degeneration (CBD). A 56-year-old Japanese woman slowly developed parkinsonism, dementia, character change, followed by vertical gaze palsy and dystonia. Brain MRI demonstrated diffuse cerebral atrophy with severe shrinkage of the brain stem tegmentum. The SPECT images using 123I-IMP disclosed symmetrical hypoperfusion in the frontal lobes. She died of respiratory failure at the age of 71.Gross inspection of the brain showed diffuse, symmetrical atrophy of the cerebrum and marked atrophy of the Luysian body, globus pallidus, substantia nigra and nuclei of the brain stem tegmentum. Microscopically, neuronal loss and fibrillary gliosis were observed in the Luysian body, globus pallidus, substantia nigra and nuclei of the brain stem tegmentum. The cerebellar dentate nucleus showed mild neuronal loss with some grumose degeneration. neurofibrillary tangles were found only in the Luysian body, substantia nigra and raphe nuclei, whilst tau-positive inclusions were observed more extensively. Astrocytic plaques and swollen achromatic neurones were found in the postcentral gyrus. There were no tuft-shaped astrocytes in the brain. The clinicopathological similarities and differences between PSP and CBD are discussed.- - - - - - - - - - ranking = 0.75keywords = neuron (Clic here for more details about this article) |
5/65. A case of frontotemporal dementia and parkinsonism of early onset with progressive supranuclear palsy-like features.We report a patient with frontotemporal degeneration and parkinsonism with mental retardation. The patient was a 54-year-old man who had parkinsonism that resembled progressive supranuclear palsy, frontotemporal degeneration and myoclonus. His family included many affected members. Neuropathologically, there was degeneration of the frontal and temporal cortices, the basal ganglia, the brainstem and the cerebellum. Microscopically, neuronal loss was severe in the frontal and temporal cortex, the globus pallidus, substantia nigra, red nucleus and dentate nucleus. Fibrillary changes were found in neurons and glia that were immunostained for tau. Although we could not define the genetic abnormalities, we thought that this case might have involved frontotemporal dementia and parkinsonism linked to chromosome 17.- - - - - - - - - - ranking = 0.5keywords = neuron (Clic here for more details about this article) |
6/65. Corticobasal syndrome with tau pathology.Six cases with a clinical corticobasal syndrome (progressive asymmetric apraxia and parkinsonism unresponsive to levodopa) and tau pathology were selected from 97 brain donors with parkinsonism. Postmortem volumetric measures of regional brain atrophy (compared with age/sex-matched controls) were correlated with clinical features and the degree of underlying cortical and subcortical histopathology. At death, no significant asymmetry of pathology was detected. All cases had prominent bilateral atrophy of the precentral gyrus (reduced by 22-54%) with other cortical regions variably affected. Subcortical atrophy was less severe and variable. Two cases demonstrated widespread atrophy of basal ganglia structures (44-60% atrophy of the internal globus pallidus) and substantial subcortical pathology consistent with a diagnosis of progressive supranuclear palsy (PSP). The remaining four cases had typical pathology of corticobasal degeneration. In all cases, neuronal loss and gliosis corresponded with subcortical atrophy, while the density of cortical swollen neurons correlated with cortical volume loss. Atrophy of the internal globus pallidus was associated with postural instability, while widespread basal ganglia histopathology was found in cases with gaze palsy. This study confirms the involvement of the precentral gyrus in the corticobasal syndrome and highlights the variable underlying pathology in these patients.- - - - - - - - - - ranking = 0.5keywords = neuron (Clic here for more details about this article) |
7/65. Tau accumulation in a patient with pallidonigroluysian atrophy.We studied the brain of a patient with pallidonigroluysian atrophy (PNLA) in whom argyrophilic and abnormally phosphorylated tau positive neurons and glia were identified in the brain on Gallyas-Braak silver staining and immunohistochemical analysis although neurofibrillary tangles were not seen by Bodian silver stain. Immunohistochemical studies using six anti-tau antibodies that recognize the different phosphorylated epitopes of tau protein revealed that these epitopes in neurons and glial cells share common characteristics with neurofibrillary tangles in Alzheimer's disease. Immunoblot analysis of phosphorylated tau protein showed major bands of 64 and 68 kDa and after dephosphorylation, tau consisted mainly of 4 repeat tau. No mutations were detected in the coding exons and their flanking intronic regions of the tau gene. This study suggests that PNLA is one of tauopathy and the biochemical characteristics of phosphorylated tau are similar to those found in progressive supranuclear palsy and corticobasal degeneration.- - - - - - - - - - ranking = 0.5keywords = neuron (Clic here for more details about this article) |
8/65. Progressive supranuclear palsy on guam.This is the first report demonstrating that progressive supranuclear palsy (PSP) exists on guam. This 75-year-old Guamanian Chamorro patient with slight dementia and rigidity with restriction of ocular up gaze was diagnosed as parkinsonism-dementia complex (PDC) of guam clinically. However, neurofibrillary tangles (NFTs) were scarcely seen in the cerebral cortices and hippocampus, but many NFTs, composed of 15-17 nm straight tubules, were detected in the subthalamic nucleus and brain stem. A large number of tuft-shaped astrocytes were observed in the putamen and motor cortex, and numerous argyrophilic grains were seen in the CA1 and subiculum. These pathological findings are different from those of PDC and consistent with PSP. The present case indicates that PSP and PDC clinically resemble each other, and that precise neuropathological examination is indispensable for the final diagnosis of the patient with parkinsonism, dementia and disturbance of vertical external ocular movement.- - - - - - - - - - ranking = 0.0058145679750962keywords = motor (Clic here for more details about this article) |
9/65. Mixed multiple system atrophy and progressive supranuclear palsy: a clinical and pathological report of one case.We report a patient who showed pathological features of both multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) at autopsy. The clinical features included severe cerebellar ataxia, autonomic failure, and rigid-akinetic parkinsonism. The clinical diagnosis was MSA. Pathological examination showed severe neuronal loss with gliosis in the putamen, substantia nigra, inferior olive, and the pontine nucleus, and numerous glial cytoplasmic inclusions. In addition, moderate neuronal loss with gliosis was observed in the globus pallidus and subthalamic nucleus, and neurofibrillary tangles and tufted astrocytes were seen in the basal ganglia and the brain stem. These findings indicate that the patient had both MSA and PSP. Double-labeling immunofluorescence in the brain stem showed alpha-synuclein immunoreactivity localized in the oligodendrocytes and phosphorylated tau immunoreactivity in the neurons and the glia. Co-existence of synucleinopathy and tauopathy is rare.- - - - - - - - - - ranking = 0.75keywords = neuron (Clic here for more details about this article) |
10/65. The pathology of the spinal cord in progressive supranuclear palsy.We describe the results of a study of the spinal cord of 5 patients with progressive supranuclear palsy (PSP). Examination of the 6th cervical, 7th thoracic, and 5th lumbar segments revealed variable degree of gliosis and density of neuropil threads (NTs), nerve cell loss, and tau-positive cytoplasmic staining of neurons, some of which was reminiscent of neurofibrillary tangles (NFT). Tau-positive neurons were seen at each spinal level and in the 3 zones in which each level was subdivided. cells with the appearance of NFT predominated in the intermediate zone. Morphometric study revealed 47%, 52%, and 32% decrease in cell numbers in the motor area (lamina IX) at the 3 spinal levels, respectively, and 39% in the intermedio-lateral column. This is the first report describing severe neuronal loss throughout the whole spinal cord in patients with PSP and its results are in keeping with a previous study of the nucleus of Onufrowicz. The reasons why cell loss fails to produce clinical symptoms are analyzed and the clinico-pathological correlations between anatomical changes and dystonia are considered. On the basis of existing data, we conclude that previous suggestions implicating spinal interneurons in the pathogenesis of neck dystonia should not be supported.- - - - - - - - - - ranking = 1.0058145679751keywords = neuron, motor (Clic here for more details about this article) |
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